Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma
Abstract
:1. Introduction
1.1. Apoptosis
1.1.1. Apoptosis Pathways
1.1.2. Extrinsic pathway
1.1.3. Intrinsic Pathway
1.1.4. Apoptosis in Glioma
1.2. Autophagy
1.2.1. Molecular Mechanisms in Autophagy
1.2.2. Autophagy in Glioma
1.2.3. Autophagy as a Tumor Suppressor
1.2.4. Autophagy as a Tumor Promoter
1.3. Molecular Correlation between Apoptosis and Autophagy
1.4. Treatment Choices for Glioblastoma
Standard of Care
1.5. Small-Molecule Inhibitors
1.5.1. Erlotinib
1.5.2. Gefitinib
1.5.3. Imatinib
1.5.4. Sunitinib
1.5.5. Vandetanib
1.6. Targeting Downstream Intracellular Effector Molecules
1.6.1. The RAS/RAF/MAPK Pathway
Tipifarnib
Lonafarnib
1.6.2. Targeting PI3K/AKT/mTOR
Temsirolimus
Everolimus
Sirolimus
1.7. Bcl-2 Inhibitors
1.7.1. ABT-737
1.7.2. Gossypol
1.7.3. Berberine
1.8. TRAIL/TRAILR Pathway Activators
1.8.1. Recombinant TRAIL, sTRAIL, and Anti-DR4 and -5 Antibodies
1.8.2. Taxol
1.8.3. TIC10/ONC201
2. Conclusions
Funding
Conflicts of Interest
Abbreviations
3 MA | methyladenine |
Activating factor-1 | Apaf-1 |
Activating transcription factor 4 | ATF4 |
Activator of transcription-3 | STAT3 |
Adenosine triphosphate | ATP |
AMBRA-1 | Activating Molecule in Beclin 1-Regulated Autophagy |
AMP-activated kinase | AMPK |
Apoptosis-inducing factor | AIF |
Autophagy-related genes | ATG |
Ataxia telangiectasia mutated protein | ATM |
ATP-binding cassette (ABC) transporters | ABCG |
Bax-interacting factor 1 | Bif-1 |
B cell lymphoma 2 | Bcl-2 |
B cell lymphoma-extra-large | Bcl-xL |
BH3-type proteins in the Bcl-2 family | BNIP3 |
Binding Protein Homology Protein | CHOP |
Ca2+/calmodulin-dependent kinase kinase | CaMKKβ |
Calcium channel, voltage-dependent gamma subunit 4 | CACNG4 |
Calcineurin-dependent 1 | NFATC1 |
Caspase recruitment domain | CARD |
Caveolin-1 | Cav-1 |
Central nervous system | CNS |
c-Jun N-terminal kinase | JNK |
Coat protein complex II | COPII |
Colony-stimulating factor-1 | CSF1R |
C vacuolar protein | C-VPS |
Cytochrome c | cyt c |
Death effector domain | DED |
Death Domain | DD |
Death-inducing signaling complex | DISC |
Diffuse Intrinsic Pontine Gliomas | DIPG |
DNA damage-regulated autophagy modulator | DRAM |
Elongation factor-2 | elF2α |
Elongation factor-2 kinase | eEF2 kinase |
Epidermal growth factor receptor | EGFR |
EGFR-targeted diphtheria toxin | DT-EGF |
Extracellular matrix | ECM |
Farnesyltransferase inhibitors | FTIs |
Fas-associated death domain | FADD |
Fas ligand | Fas-L |
Fas receptor | FasR |
Fibroblast growth factor receptor 4 | FGFR4 |
FK-binding protein-12 | FKBP-12 |
Fms-like tyrosine kinase-3 | FLT3 |
Focal adhesion kinase | FAK |
Food and Drug Administration | FDA |
G protein β-subunit-like protein | GβL |
Glioblastoma multiforme | GBM |
Glioma Stem Cells | GSC |
Glioma stem/progenitor cells | GSPCs |
Heat shock cognate 71 kDa protein | Hsc70 |
Heat shock 27-kD protein 1 | HSPB1 |
Heat shock 70-kD protein 1B | HSPA1B |
High-mobility group box protein 1 | HMGB1 |
Human multidrug resistance protein 3 | MRP3 |
Inhibitor of apoptosis | IAP |
Inositol 1,4,5-triphosphate receptor | IP3R |
Lysosomal-associate membrane protein 2A receptor | LAMP2A |
Methylguanine-O6-methyltransferase | MGMT |
Mitogen-activated protein kinase | MAPK |
Monocarboxylate transporter-4 | MCT4 |
Neurotrophic tyrosine kinase receptor type-1 | NTRK1 |
Nitrogen reactive species | NOS |
Overall survival | OS |
Paxillin | PXN |
Phagophore assembly site | PAS |
Phosphatidylinositol 3-phosphate | PI3P |
Phosphatidylinositol-4,5-bisphosphate | PIP2 |
Phosphatidylinositol-3,4,5-trisphosphate | PIP3 |
Phosphatidylethanolamine | PE |
Phospholipase C-γ1 | PLC-γ1 |
Platelet-derived growth factor receptor | PDGR |
Proline-rich AKT substrate of 40 kDa | PRAS40 |
Progression-free survival | PFS |
Protein endoplasmic reticulum kinase | PERK |
RAS-related C3 botulinum toxin substrate 1 | RAC1 |
Reactive oxygen species | ROS |
Ribosomal S6 kinase 1 | RSK1 |
Second Mitochondria-derived Activator of Caspases | Smac |
Direct IAP-Binding protein with Low PI | DIABLO |
Serine/threonine kinases phosphoinositide-dependent kinase 1 | PDK1 |
Stem cell-factor | Kit |
Smoothened homolog | SMO |
Target of rapamycin complex 1 | TORC1 |
Temozolomide | TMZ |
Tyrosine-kinase inhibitors | TKI |
Transcription factor 7-like 1 | TCF7L1 |
Transforming growth factor beta 3 | TGFβ3 |
Transforming growth factor-β-activating kinase 1 | TAK1 |
Tensin homolog on chromosome ten | PTEN |
Toll-like receptor 4 | TLR4 |
Transport protein particle III | TRAPPIII |
Tumor Necrosis Factor receptors | TNF |
Tumor Necrosis Factor receptors | TNFR |
Tumor necrosis factor-related apoptosis-inducing ligand | TRAIL |
Unc-51-Like Kinase ½ | ULK1/ULK2 |
UV irradiation resistance-associated tumor suppressor gene | UVRAG |
Vascular endothelial growth factor receptor | VEGFR |
References
- DeAngelis, L.M. Brain tumors. N. Engl. J. Med. 2001, 344, 114–123. [Google Scholar] [CrossRef] [PubMed]
- Crocetti, E.; Trama, A.; Stiller, C.; Caldarella, A.; Soffietti, R.; Jaal, J.; Weber, D.C.; Ricardi, U.; Slowinski, J.; Brandes, A.; et al. Epidemiology of glial and non-glial brain tumours in Europe. Eur. J. Cancer 2012, 48, 1532–1542. [Google Scholar] [CrossRef] [PubMed]
- Budke, M.; Isla-Guerrero, A.; Perez-Lopez, C.; Perez-Alvarez, M.; Garcia-Grande, A.; Bello, M.J.; Rey, J. A comparative study of the treatment of high grade gliomas. Rev. Neurol. 2003, 37, 912–916. [Google Scholar] [PubMed]
- Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007, 114, 97–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grobben, B.; De Deyn, P.P.; Slegers, H. Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res. 2002, 310, 257–270. [Google Scholar] [CrossRef] [PubMed]
- Mischel, P.S.; Cloughesy, T.F. Targeted molecular therapy of GBM. Brain Pathol. 2003, 13, 52–61. [Google Scholar] [CrossRef] [PubMed]
- Voldborg, B.R.; Damstrup, L.; Spang-Thomsen, M.; Poulsen, H.S. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann. Oncol. 1997, 8, 1197–1206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Katz, A.M.; Amankulor, N.M.; Pitter, K.; Helmy, K.; Squatrito, M.; Holland, E.C. Astrocyte-specific expression patterns associated with the PDGF-induced glioma microenvironment. PLoS ONE 2012, 7, e32453. [Google Scholar] [CrossRef] [PubMed]
- Machein, M.R.; Plate, K.H. VEGF in brain tumors. J. Neuro-Oncol. 2000, 50, 109–120. [Google Scholar] [CrossRef]
- Feldkamp, M.M.; Lau, N.; Guha, A. Signal transduction pathways and their relevance in human astrocytomas. J. Neuro-Oncol. 1997, 35, 223–248. [Google Scholar] [CrossRef]
- Chakravarti, A.; Delaney, M.A.; Noll, E.; Black, P.M.; Loeffler, J.S.; Muzikansky, A.; Dyson, N.J. Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas. Clin. Cancer Res. 2001, 7, 2387–2395. [Google Scholar] [PubMed]
- Kornienko, A.; Mathieu, V.; Rastogi, S.K.; Lefranc, F.; Kiss, R. Therapeutic agents triggering nonapoptotic cancer cell death. J. Med. Chem. 2013, 56, 4823–4839. [Google Scholar] [CrossRef] [PubMed]
- Djedid, R.; Tomasi, O.; Haidara, A.; Rynkowski, M.; Lefranc, F. Glioblastoma treatment in 2010. Rev. Med. Brux. 2009, 30, 496–505. [Google Scholar] [PubMed]
- Trejo-Solis, C.; Jimenez-Farfan, D.; Rodriguez-Enriquez, S.; Fernandez-Valverde, F.; Cruz-Salgado, A.; Ruiz-Azuara, L.; Sotelo, J. Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and JNK activation. BMC Cancer 2012, 12, 156. [Google Scholar] [CrossRef] [PubMed]
- Tiwari, M.; Bajpai, V.K.; Sahasrabuddhe, A.A.; Kumar, A.; Sinha, R.A.; Behari, S.; Godbole, M.M. Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells. Carcinogenesis 2008, 29, 600–609. [Google Scholar] [CrossRef] [PubMed]
- Jo, G.H.; Bogler, O.; Chwae, Y.J.; Yoo, H.; Lee, S.H.; Park, J.B.; Kim, Y.J.; Kim, J.H.; Gwak, H.S. Radiation-induced autophagy contributes to cell death and induces apoptosis partly in malignant glioma cells. Cancer Res. Treat. 2015, 47, 221–241. [Google Scholar] [CrossRef] [PubMed]
- Thayyullathil, F.; Rahman, A.; Pallichankandy, S.; Patel, M.; Galadari, S. ROS-dependent prostate apoptosis response-4 (Par-4) up-regulation and ceramide generation are the prime signaling events associated with curcumin-induced autophagic cell death in human malignant glioma. FEBS Open Bio 2014, 4, 763–776. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keshmiri-Neghab, H.; Goliaei, B.; Nikoofar, A. Gossypol enhances radiation induced autophagy in glioblastoma multiforme. Gen. Physiol. Biophys. 2014, 33, 433–442. [Google Scholar] [CrossRef] [PubMed]
- Kerr, J.F.; Wyllie, A.H.; Currie, A.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 1972, 26, 239–257. [Google Scholar] [CrossRef] [PubMed]
- Serrano-Garcia, N.; Pedraza-Chaverri, J.; Mares-Samano, J.J.; Orozco-Ibarra, M.; Cruz-Salgado, A.; Jimenez-Anguiano, A.; Sotelo, J.; Trejo-Solis, C. Antiapoptotic Effects of EGb 761. ECAM 2013, 2013, 495703. [Google Scholar] [CrossRef] [PubMed]
- Lees, A.J.; Hardy, J.; Revesz, T. Parkinson’s disease. Lancet 2009, 373, 2055–2066. [Google Scholar] [CrossRef]
- Hunter, A.M.; LaCasse, E.C.; Korneluk, R.G. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 2007, 12, 1543–1568. [Google Scholar] [CrossRef] [PubMed]
- Ashkenazi, A.; Dixit, V.M. Death receptors: Signaling and modulation. Science 1998, 281, 1305–1308. [Google Scholar] [CrossRef] [PubMed]
- Gupta, S. Molecular steps of cell suicide: An insight into immune senescence. J. Clin. Immunol. 2000, 20, 229–239. [Google Scholar] [CrossRef] [PubMed]
- Nijhawan, D.; Honarpour, N.; Wang, X. Apoptosis in neural development and disease. Ann. Rev. Neurosci. 2000, 23, 73–87. [Google Scholar] [CrossRef] [PubMed]
- Orlinick, J.R.; Vaishnaw, A.K.; Elkon, K.B. Structure and function of Fas/Fas ligand. Int. Rev. Immunol. 1999, 18, 293–308. [Google Scholar] [CrossRef] [PubMed]
- Cahuzac, N.; Baum, W.; Kirkin, V.; Conchonaud, F.; Wawrezinieck, L.; Marguet, D.; Janssen, O.; Zornig, M.; Hueber, A.O. Fas ligand is localized to membrane rafts, where it displays increased cell death-inducing activity. Blood 2006, 107, 2384–2391. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Watanabe-Fukunaga, R.; Brannan, C.I.; Itoh, N.; Yonehara, S.; Copeland, N.G.; Jenkins, N.A.; Nagata, S. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J. Immunol. 1992, 148, 1274–1279. [Google Scholar] [PubMed]
- Bechmann, I.; Mor, G.; Nilsen, J.; Eliza, M.; Nitsch, R.; Naftolin, F. FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: Evidence for the existence of an immunological brain barrier. Glia 1999, 27, 62–74. [Google Scholar] [CrossRef]
- Choi, C.; Park, J.Y.; Lee, J.; Lim, J.H.; Shin, E.C.; Ahn, Y.S.; Kim, C.H.; Kim, S.J.; Kim, J.D.; Choi, I.S.; et al. Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-alpha, or IFN-gamma. J. Immunol. 1999, 162, 1889–1895. [Google Scholar] [PubMed]
- MacEwan, D.J. TNF ligands and receptors—A matter of life and death. Br. J. Pharmacol. 2002, 135, 855–875. [Google Scholar] [CrossRef] [PubMed]
- Lambert, C.; Landau, A.M.; Desbarats, J. Fas-beyond death: A regenerative role for Fas in the nervous system. Apoptosis 2003, 8, 551–562. [Google Scholar] [CrossRef] [PubMed]
- Scaffidi, C.; Kischkel, F.C.; Krammer, P.H.; Peter, M.E. Analysis of the CD95 (APO-1/Fas) death-inducing signaling complex by high-resolution two-dimensional gel electrophoresis. Methods Enzymol. 2000, 322, 363–373. [Google Scholar] [PubMed]
- Zhang, J.; Zhang, D.; Hua, Z. FADD and its phosphorylation. IUBMB Life 2004, 56, 395–401. [Google Scholar] [CrossRef] [PubMed]
- Gomez-Angelats, M.; Cidlowski, J.A. Molecular evidence for the nuclear localization of FADD. Cell Death Differ. 2003, 10, 791–797. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Forbes-Hernandez, T.Y.; Giampieri, F.; Gasparrini, M.; Mazzoni, L.; Quiles, J.L.; Alvarez-Suarez, J.M.; Battino, M. The effects of bioactive compounds from plant foods on mitochondrial function: A focus on apoptotic mechanisms. Food Chem. Toxicol. 2014, 68, 154–182. [Google Scholar] [CrossRef] [PubMed]
- Mohr, A.; Deedigan, L.; Jencz, S.; Mehrabadi, Y.; Houlden, L.; Albarenque, S.M.; Zwacka, R.M. Caspase-10: A molecular switch from cell-autonomous apoptosis to communal cell death in response to chemotherapeutic drug treatment. Cell Death Differ. 2018, 25, 340–352. [Google Scholar] [CrossRef] [PubMed]
- Wu, C.S.; Chen, G.S.; Lin, P.Y.; Pan, I.H.; Wang, S.T.; Lin, S.H.; Yu, H.S.; Lin, C.C. Tazarotene induces apoptosis in human basal cell carcinoma via activation of caspase-8/t-Bid and the reactive oxygen species-dependent mitochondrial pathway. DNA Cell Biol. 2014, 33, 652–666. [Google Scholar] [CrossRef] [PubMed]
- Sastry, P.S.; Rao, K.S. Apoptosis and the nervous system. J. Neurochem. 2000, 74, 1–20. [Google Scholar] [CrossRef] [PubMed]
- Ashe, P.C.; Berry, M.D. Apoptotic signaling cascades. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2003, 27, 199–214. [Google Scholar] [CrossRef]
- Zimmermann, K.C.; Bonzon, C.; Green, D.R. The machinery of programmed cell death. Pharmacol. Ther. 2001, 92, 57–70. [Google Scholar] [CrossRef]
- Adams, J.M.; Cory, S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998, 281, 1322–1326. [Google Scholar] [CrossRef] [PubMed]
- Hockenbery, D.M. Targeting mitochondria for cancer therapy. Environ. Mol. Mutagen. 2010, 51, 476–489. [Google Scholar] [CrossRef] [PubMed]
- Moroni, M.C.; Hickman, E.S.; Lazzerini Denchi, E.; Caprara, G.; Colli, E.; Cecconi, F.; Muller, H.; Helin, K. Apaf-1 is a transcriptional target for E2F and p53. Nat. Cell Biol. 2001, 3, 552–558. [Google Scholar] [CrossRef] [PubMed]
- Angosto, M. Bases Moleculares de la Apoptosis. Anal. Real Acad. Nac. Farm. 2003, 69, 29. [Google Scholar]
- Verhagen, A.M.; Silke, J.; Ekert, P.G.; Pakusch, M.; Kaufmann, H.; Connolly, L.M.; Day, C.L.; Tikoo, A.; Burke, R.; Wrobel, C.; et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem. 2002, 277, 445–454. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.E.-D. Cell Cycle Arrest and Apoptosis; Springer: Dordrecht, The Netherlands, 2007. [Google Scholar]
- Wu, G.S.; Burns, T.F.; McDonald, E.R., 3rd; Jiang, W.; Meng, R.; Krantz, I.D.; Kao, G.; Gan, D.D.; Zhou, J.Y.; Muschel, R.; et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat. Genet. 1997, 17, 141–143. [Google Scholar] [CrossRef] [PubMed]
- Levine, B.; Sinha, S.C.; Kroemer, G. Bcl-2 family members: Dual regulators of apoptosis and autophagy. Autophagy 2008, 4, 600–606. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Amaral, J.D.; Xavier, J.M.; Steer, C.J.; Rodrigues, C.M. The role of p53 in apoptosis. Discov. Med. 2010, 9, 145–152. [Google Scholar] [PubMed]
- Altin, S.E.; Schulze, P.C. p53-upregulated modulator of apoptosis (PUMA): A novel proapoptotic molecule in the failing heart. Circulation 2011, 124, 7–8. [Google Scholar] [CrossRef] [PubMed]
- Strozyk, E.; Kulms, D. The role of AKT/mTOR pathway in stress response to UV-irradiation: Implication in skin carcinogenesis by regulation of apoptosis, autophagy and senescence. Int. J. Mol. Sci. 2013, 14, 15260–15285. [Google Scholar] [CrossRef] [PubMed]
- Peltonen, J.K.; Vahakangas, K.H.; Helppi, H.M.; Bloigu, R.; Paakko, P.; Turpeenniemi-Hujanen, T. Specific TP53 mutations predict aggressive phenotype in head and neck squamous cell carcinoma: A retrospective archival study. Head Neck Oncol. 2011, 3, 20. [Google Scholar] [CrossRef] [PubMed]
- Kalimuthu, S.; Se-Kwon, K. Cell survival and apoptosis signaling as therapeutic target for cancer: Marine bioactive compounds. Int. J. Mol. Sci. 2013, 14, 2334–2354. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Jiang, Y.; Meisenhelder, J.; Yang, W.; Hawke, D.H.; Zheng, Y.; Xia, Y.; Aldape, K.; He, J.; Hunter, T.; et al. Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. Mol. Cell 2016, 61, 705–719. [Google Scholar] [CrossRef] [PubMed]
- Tsuruta, F.; Sunayama, J.; Mori, Y.; Hattori, S.; Shimizu, S.; Tsujimoto, Y.; Yoshioka, K.; Masuyama, N.; Gotoh, Y. JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004, 23, 1889–1899. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krakstad, C.; Chekenya, M. Survival signalling and apoptosis resistance in glioblastomas: Opportunities for targeted therapeutics. Mol. Cancer 2010, 9, 135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stegh, A.H.; Kim, H.; Bachoo, R.M.; Forloney, K.L.; Zhang, J.; Schulze, H.; Park, K.; Hannon, G.J.; Yuan, J.; Louis, D.N.; et al. Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev. 2007, 21, 98–111. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wick, W.; Wagner, S.; Kerkau, S.; Dichgans, J.; Tonn, J.C.; Weller, M. BCL-2 promotes migration and invasiveness of human glioma cells. FEBS Lett. 1998, 440, 419–424. [Google Scholar] [CrossRef] [Green Version]
- Wick, W.; Wild-Bode, C.; Frank, B.; Weller, M. BCL-2-induced glioma cell invasiveness depends on furin-like proteases. J. Neurochem. 2004, 91, 1275–1283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tyagi, D.; Sharma, B.S.; Gupta, S.K.; Kaul, D.; Vasishta, R.K.; Khosla, V.K. Expression of Bcl2 proto-oncogene in primary tumors of the central nervous system. Neurol. India 2002, 50, 290–294. [Google Scholar] [PubMed]
- Steinbach, J.P.; Weller, M. Apoptosis in Gliomas: Molecular Mechanisms and Therapeutic Implications. J. Neuro-Oncol. 2004, 70, 247–256. [Google Scholar] [CrossRef] [PubMed]
- Strik, H.; Deininger, M.; Streffer, J.; Grote, E.; Wickboldt, J.; Dichgans, J.; Weller, M.; Meyermann, R. BCL-2 family protein expression in initial and recurrent glioblastomas: Modulation by radiochemotherapy. J. Neurol. Neurosurg. Psychiatry 1999, 67, 763–768. [Google Scholar] [CrossRef] [PubMed]
- Ruano, Y.; Mollejo, M.; Camacho, F.I.; Rodriguez de Lope, A.; Fiano, C.; Ribalta, T.; Martinez, P.; Hernandez-Moneo, J.L.; Melendez, B. Identification of survival-related genes of the phosphatidylinositol 3’-kinase signaling pathway in glioblastoma multiforme. Cancer 2008, 112, 1575–1584. [Google Scholar] [CrossRef] [PubMed]
- Cartron, P.F.; Loussouarn, D.; Campone, M.; Martin, S.A.; Vallette, F.M. Prognostic impact of the expression/phosphorylation of the BH3-only proteins of the BCL-2 family in glioblastoma multiforme. Cell Death Dis. 2012, 3, e421. [Google Scholar] [CrossRef] [PubMed]
- Blahovcova, E.; Richterova, R.; Kolarovszki, B.; Dobrota, D.; Racay, P.; Hatok, J. Apoptosis-related gene expression in tumor tissue samples obtained from patients diagnosed with glioblastoma multiforme. Int. J. Mol. Med. 2015, 36, 1677–1684. [Google Scholar] [CrossRef] [PubMed]
- Murphy, A.C.; Weyhenmeyer, B.; Schmid, J.; Kilbride, S.M.; Rehm, M.; Huber, H.J.; Senft, C.; Weissenberger, J.; Seifert, V.; Dunst, M.; et al. Activation of executioner caspases is a predictor of progression-free survival in glioblastoma patients: A systems medicine approach. Cell Death Dis. 2013, 4, e629. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.B.; Li, T.; Ma, D.Z.; Ji, Y.X.; Zhi, H. Overexpression of FADD and Caspase-8 inhibits proliferation and promotes apoptosis of human glioblastoma cells. Biomed. Pharmacother. 2017, 93, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Saggioro, F.P.; Neder, L.; Stavale, J.N.; Paixao-Becker, A.N.; Malheiros, S.M.; Soares, F.A.; Pittella, J.E.; Matias, C.C.; Colli, B.O.; Carlotti, C.G., Jr.; et al. Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: A tissue microarray-based study. Pathol. Res. Pract. 2014, 210, 267–273. [Google Scholar] [CrossRef] [PubMed]
- Ashley, D.M.; Riffkin, C.D.; Muscat, A.M.; Knight, M.J.; Kaye, A.H.; Novak, U.; Hawkins, C.J. Caspase 8 is absent or low in many ex vivo gliomas. Cancer 2005, 104, 1487–1496. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Knight, M.J.; Riffkin, C.D.; Muscat, A.M.; Ashley, D.M.; Hawkins, C.J. Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene 2001, 20, 5789–5798. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuijlen, J.M.; Mooij, J.J.; Platteel, I.; Hoving, E.W.; van der Graaf, W.T.; Span, M.M.; Hollema, H.; den Dunnen, W.F. TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme. J. Neuro-Oncol. 2006, 78, 161–171. [Google Scholar] [CrossRef] [PubMed]
- Elias, A.; Siegelin, M.D.; Steinmuller, A.; von Deimling, A.; Lass, U.; Korn, B.; Mueller, W. Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin. Cancer Res. 2009, 15, 5457–5465. [Google Scholar] [CrossRef] [PubMed]
- Wagenknecht, B.; Glaser, T.; Naumann, U.; Kugler, S.; Isenmann, S.; Bahr, M.; Korneluk, R.; Liston, P.; Weller, M. Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma. Cell Death Differ. 1999, 6, 370–376. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takeshige, K.; Baba, M.; Tsuboi, S.; Noda, T.; Ohsumi, Y. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J. Cell Biol. 1992, 119, 301–311. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ryter, S.W.; Cloonan, S.M.; Choi, A.M. Autophagy: A critical regulator of cellular metabolism and homeostasis. Mol. Cells 2013, 36, 7–16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaur, J.; Debnath, J. Autophagy at the crossroads of catabolism and anabolism. Nat. Rev. Mol. Cell Biol. 2015, 16, 461–472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuma, A.; Hatano, M.; Matsui, M.; Yamamoto, A.; Nakaya, H.; Yoshimori, T.; Ohsumi, Y.; Tokuhisa, T.; Mizushima, N. The role of autophagy during the early neonatal starvation period. Nature 2004, 432, 1032–1036. [Google Scholar] [CrossRef] [PubMed]
- Jiang, P.; Mizushima, N. Autophagy and human diseases. Cell Res. 2014, 24, 69–79. [Google Scholar] [CrossRef] [PubMed]
- White, E.; Karp, C.; Strohecker, A.M.; Guo, Y.; Mathew, R. Role of autophagy in suppression of inflammation and cancer. Curr. Opin. Cell Biol. 2010, 22, 212–217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell 2008, 132, 27–42. [Google Scholar] [CrossRef] [PubMed]
- Juhasz, G.; Neufeld, T.P. Autophagy: A forty-year search for a missing membrane source. PLoS Biol. 2006, 4, e36. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maiuri, M.C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2007, 8, 741–752. [Google Scholar] [CrossRef] [PubMed]
- Marino, G.; Niso-Santano, M.; Baehrecke, E.H.; Kroemer, G. Self-consumption: The interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2014, 15, 81–94. [Google Scholar] [CrossRef] [PubMed]
- Mathew, R.; Karp, C.M.; Beaudoin, B.; Vuong, N.; Chen, G.; Chen, H.Y.; Bray, K.; Reddy, A.; Bhanot, G.; Gelinas, C.; et al. Autophagy suppresses tumorigenesis through elimination of p62. Cell 2009, 137, 1062–1075. [Google Scholar] [CrossRef] [PubMed]
- Chu, P.M.; Chen, L.H.; Chen, M.T.; Ma, H.I.; Su, T.L.; Hsieh, P.C.; Chien, C.S.; Jiang, B.H.; Chen, Y.C.; Lin, Y.H.; et al. Targeting autophagy enhances BO-1051-induced apoptosis in human malignant glioma cells. Cancer Chemother. Pharmacol. 2012, 69, 621–633. [Google Scholar] [CrossRef] [PubMed]
- Van Beek, N.; Klionsky, D.J.; Reggiori, F. Genetic aberrations in macroautophagy genes leading to diseases. Biochim. Biophys. Acta Mol. Cell Res. 2018, 1865, 803–816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Giampieri, F.; Afrin, S.; Forbes-Hernandez, T.Y.; Gasparrini, M.; Cianciosi, D.; Reboredo-Rodriguez, P.; Varela-Lopez, A.; Quiles, J.L.; Battino, M. Autophagy in Human Health and Disease: Novel Therapeutic Opportunities. Antioxid. Redox Signal. 2018. [Google Scholar] [CrossRef] [PubMed]
- Klionsky, D.J.; Abdelmohsen, K.; Abe, A.; Abedin, M.J.; Abeliovich, H.; Acevedo Arozena, A.; Adachi, H.; Adams, C.M.; Adams, P.D.; Adeli, K.; et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 2016, 12, 1–222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oku, M.; Sakai, Y. Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries. BioEssays 2018, 40, e1800008. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, K.; Akioka, M.; Kondo-Kakuta, C.; Yamamoto, H.; Ohsumi, Y. Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae. J. Cell Sci. 2013, 126, 2534–2544. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Farre, J.C.; Subramani, S. Mechanistic insights into selective autophagy pathways: Lessons from yeast. Nat. Rev. Mol. Cell Biol. 2016, 17, 537–552. [Google Scholar] [CrossRef] [PubMed]
- Jung, C.H.; Jun, C.B.; Ro, S.H.; Kim, Y.M.; Otto, N.M.; Cao, J.; Kundu, M.; Kim, D.H. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 2009, 20, 1992–2003. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kundu, M.; Viollet, B.; Guan, K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 2011, 13, 132–141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morris, D.H.; Yip, C.K.; Shi, Y.; Chait, B.T.; Wang, Q.J. Beclin 1-Vps34 Complex Architecture: Understanding the Nuts and Bolts of Therapeutic Targets. Front. Biol. 2015, 10, 398–426. [Google Scholar] [CrossRef] [PubMed]
- Cao, Y.; Klionsky, D.J. Physiological functions of Atg6/Beclin 1: A unique autophagy-related protein. Cell Res. 2007, 17, 839–849. [Google Scholar] [CrossRef] [PubMed]
- Russell, R.C.; Tian, Y.; Yuan, H.; Park, H.W.; Chang, Y.Y.; Kim, J.; Kim, H.; Neufeld, T.P.; Dillin, A.; Guan, K.L. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat. Cell Biol. 2013, 15, 741–750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Polson, H.E.; de Lartigue, J.; Rigden, D.J.; Reedijk, M.; Urbe, S.; Clague, M.J.; Tooze, S.A. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 2010, 6, 506–522. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Law, F.; Seo, J.H.; Wang, Z.; DeLeon, J.L.; Bolis, Y.; Brown, A.; Zong, W.X.; Du, G.; Rocheleau, C.E. The VPS34 PI3K negatively regulates RAB-5 during endosome maturation. J. Cell Sci. 2017, 130, 2007–2017. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mari, M.; Tooze, S.A.; Reggiori, F. The puzzling origin of the autophagosomal membrane. F1000 Biol. Rep. 2011, 3, 25. [Google Scholar] [CrossRef] [PubMed]
- Wild, P.; McEwan, D.G.; Dikic, I. The LC3 interactome at a glance. J. Cell Sci. 2014, 127, 3–9. [Google Scholar] [CrossRef]
- Monastyrska, I.; Rieter, E.; Klionsky, D.J.; Reggiori, F. Multiple roles of the cytoskeleton in autophagy. Biol. Rev. Camb. Philos. Soc. 2009, 84, 431–448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Metcalf, D.; Isaacs, A.M. The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. Biochem. Soc. Trans. 2010, 38, 1469–1473. [Google Scholar] [CrossRef] [PubMed]
- Hasselbalch, H.C. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development? Leuk. Res. 2013, 37, 214–220. [Google Scholar] [CrossRef] [PubMed]
- Laplante, M.; Sabatini, D.M. mTOR signaling at a glance. J. Cell Sci. 2009, 122, 3589–3594. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nazio, F.; Strappazzon, F.; Antonioli, M.; Bielli, P.; Cianfanelli, V.; Bordi, M.; Gretzmeier, C.; Dengjel, J.; Piacentini, M.; Fimia, G.M.; et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat. Cell Biol. 2013, 15, 406–416. [Google Scholar] [CrossRef] [PubMed]
- Platta, H.W.; Abrahamsen, H.; Thoresen, S.B.; Stenmark, H. Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1. Biochem. J. 2012, 441, 399–406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, C.C.; Lin, Y.C.; Chen, Y.H.; Chen, C.M.; Pang, L.Y.; Chen, H.A.; Wu, P.R.; Lin, M.Y.; Jiang, S.T.; Tsai, T.F.; et al. Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. Mol. Cell 2016, 61, 84–97. [Google Scholar] [CrossRef] [PubMed]
- Martina, J.A.; Chen, Y.; Gucek, M.; Puertollano, R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 2012, 8, 903–914. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laplante, M.; Sabatini, D.M. Regulation of mTORC1 and its impact on gene expression at a glance. J. Cell Sci. 2013, 126, 1713–1719. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hardie, D.G. AMPK and autophagy get connected. EMBO J. 2011, 30, 634–635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, Y.; Yang, J.; Liao, W.; Liu, X.; Zhang, H.; Wang, S.; Wang, D.; Feng, J.; Yu, L.; Zhu, W.G. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat. Cell Biol. 2010, 12, 665–675. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kim, Y.C.; Fang, C.; Russell, R.C.; Kim, J.H.; Fan, W.; Liu, R.; Zhong, Q.; Guan, K.L. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell 2013, 152, 290–303. [Google Scholar] [CrossRef] [PubMed]
- Maiuri, M.C.; Le Toumelin, G.; Criollo, A.; Rain, J.C.; Gautier, F.; Juin, P.; Tasdemir, E.; Pierron, G.; Troulinaki, K.; Tavernarakis, N.; et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 2007, 26, 2527–2539. [Google Scholar] [CrossRef] [PubMed]
- Mathew, R.; Karantza-Wadsworth, V.; White, E. Role of autophagy in cancer. Nat. Rev. Cancer 2007, 7, 961–967. [Google Scholar] [CrossRef] [PubMed]
- Huang, X.; Bai, H.M.; Chen, L.; Li, B.; Lu, Y.C. Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors. J. Clin. Neurosci. 2010, 17, 1515–1519. [Google Scholar] [CrossRef] [PubMed]
- Pirtoli, L.; Cevenini, G.; Tini, P.; Vannini, M.; Oliveri, G.; Marsili, S.; Mourmouras, V.; Rubino, G.; Miracco, C. The prognostic role of Beclin 1 protein expression in high-grade gliomas. Autophagy 2009, 5, 930–936. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shukla, S.; Patric, I.R.; Patil, V.; Shwetha, S.D.; Hegde, A.S.; Chandramouli, B.A.; Arivazhagan, A.; Santosh, V.; Somasundaram, K. Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth. J. Biol. Chem. 2014, 289, 22306–22318. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Tian, H.; Miao, Y.; Feng, X.; Li, Y.; Wang, H.; Song, X. Upregulation of p72 Enhances Malignant Migration and Invasion of Glioma Cells by Repressing Beclin1 Expression. Biochem. Biokhimiia 2016, 81, 574–582. [Google Scholar] [CrossRef] [PubMed]
- Aoki, H.; Kondo, Y.; Aldape, K.; Yamamoto, A.; Iwado, E.; Yokoyama, T.; Hollingsworth, E.F.; Kobayashi, R.; Hess, K.; Shinojima, N.; et al. Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy 2008, 4, 467–475. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, H.; Sun, T.; Hu, J.; Zhang, R.; Rao, Y.; Wang, S.; Chen, R.; McLendon, R.E.; Friedman, A.H.; Keir, S.T.; et al. miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways. J. Clin. Investig. 2014, 124, 4489–4502. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jennewein, L.; Ronellenfitsch, M.W.; Antonietti, P.; Ilina, E.I.; Jung, J.; Stadel, D.; Flohr, L.M.; Zinke, J.; von Renesse, J.; Drott, U.; et al. Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas. Oncotarget 2016, 7, 20016–20032. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Galavotti, S.; Bartesaghi, S.; Faccenda, D.; Shaked-Rabi, M.; Sanzone, S.; McEvoy, A.; Dinsdale, D.; Condorelli, F.; Brandner, S.; Campanella, M.; et al. The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene 2013, 32, 699–712. [Google Scholar] [CrossRef] [PubMed]
- Son, Y.O.; Pratheeshkumar, P.; Roy, R.V.; Hitron, J.A.; Wang, L.; Zhang, Z.; Shi, X. Nrf2/p62 signaling in apoptosis resistance and its role in cadmium-induced carcinogenesis. J. Biol. Chem. 2014, 289, 28660–28675. [Google Scholar] [CrossRef] [PubMed]
- Degenhardt, K.; Mathew, R.; Beaudoin, B.; Bray, K.; Anderson, D.; Chen, G.; Mukherjee, C.; Shi, Y.; Gelinas, C.; Fan, Y.; et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006, 10, 51–64. [Google Scholar] [CrossRef] [PubMed]
- Apetoh, L.; Ghiringhelli, F.; Tesniere, A.; Obeid, M.; Ortiz, C.; Criollo, A.; Mignot, G.; Maiuri, M.C.; Ullrich, E.; Saulnier, P.; et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 2007, 13, 1050–1059. [Google Scholar] [CrossRef] [PubMed]
- Young, A.R.; Narita, M.; Ferreira, M.; Kirschner, K.; Sadaie, M.; Darot, J.F.; Tavare, S.; Arakawa, S.; Shimizu, S.; Watt, F.M.; et al. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009, 23, 798–803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, J.S.; Oh, E.; Yoo, J.Y.; Choi, K.S.; Yoon, M.J.; Yun, C.O. Adenovirus expressing dual c-Met-specific shRNA exhibits potent antitumor effect through autophagic cell death accompanied by senescence-like phenotypes in glioblastoma cells. Oncotarget 2015, 6, 4051–4065. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Knizhnik, A.V.; Roos, W.P.; Nikolova, T.; Quiros, S.; Tomaszowski, K.H.; Christmann, M.; Kaina, B. Survival and death strategies in glioma cells: Autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS ONE 2013, 8, e55665. [Google Scholar] [CrossRef] [PubMed]
- Lepine, S.; Allegood, J.C.; Edmonds, Y.; Milstien, S.; Spiegel, S. Autophagy induced by deficiency of sphingosine-1-phosphate phosphohydrolase 1 is switched to apoptosis by calpain-mediated autophagy-related gene 5 (Atg5) cleavage. J. Biol. Chem. 2011, 286, 44380–44390. [Google Scholar] [CrossRef] [PubMed]
- Pyo, J.O.; Jang, M.H.; Kwon, Y.K.; Lee, H.J.; Jun, J.I.; Woo, H.N.; Cho, D.H.; Choi, B.; Lee, H.; Kim, J.H.; et al. Essential roles of Atg5 and FADD in autophagic cell death: Dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 2005, 280, 20722–20729. [Google Scholar] [CrossRef] [PubMed]
- Yousefi, S.; Perozzo, R.; Schmid, I.; Ziemiecki, A.; Schaffner, T.; Scapozza, L.; Brunner, T.; Simon, H.U. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 2006, 8, 1124–1132. [Google Scholar] [CrossRef] [PubMed]
- Huang, X.; Qi, Q.; Hua, X.; Li, X.; Zhang, W.; Sun, H.; Li, S.; Wang, X.; Li, B. Beclin 1, an autophagy-related gene, augments apoptosis in U87 glioblastoma cells. Oncol. Rep. 2014, 31, 1761–1767. [Google Scholar] [CrossRef] [PubMed]
- Kaza, N.; Kohli, L.; Roth, K.A. Autophagy in brain tumors: A new target for therapeutic intervention. Brain Pathol. 2012, 22, 89–98. [Google Scholar] [CrossRef] [PubMed]
- Wu, S.T.; Sun, G.H.; Cha, T.L.; Kao, C.C.; Chang, S.Y.; Kuo, S.C.; Way, T.D. CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway. J. Biomed. Sci. 2016, 23, 60. [Google Scholar] [CrossRef] [PubMed]
- Yuan, X.; Du, J.; Hua, S.; Zhang, H.; Gu, C.; Wang, J.; Yang, L.; Huang, J.; Yu, J.; Liu, F. Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells. Exp. Cell Res. 2015, 330, 267–276. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Li, W.; Wang, C.; Leng, X.; Lian, S.; Feng, J.; Li, J.; Wang, H. Inhibition of autophagy enhances apoptosis induced by proteasome inhibitor bortezomib in human glioblastoma U87 and U251 cells. Mol. Cell. Biochem. 2014, 385, 265–275. [Google Scholar] [CrossRef] [PubMed]
- Mazure, N.M.; Pouyssegur, J. Hypoxia-induced autophagy: Cell death or cell survival? Curr. Opin. Cell Biol. 2010, 22, 177–180. [Google Scholar] [CrossRef] [PubMed]
- Bellot, G.; Garcia-Medina, R.; Gounon, P.; Chiche, J.; Roux, D.; Pouyssegur, J.; Mazure, N.M. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol. Cell. Biol. 2009, 29, 2570–2581. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.L.; DeLay, M.; Jahangiri, A.; Molinaro, A.M.; Rose, S.D.; Carbonell, W.S.; Aghi, M.K. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res. 2012, 72, 1773–1783. [Google Scholar] [CrossRef] [PubMed]
- Pavlides, S.; Vera, I.; Gandara, R.; Sneddon, S.; Pestell, R.G.; Mercier, I.; Martinez-Outschoorn, U.E.; Whitaker-Menezes, D.; Howell, A.; Sotgia, F.; et al. Warburg meets autophagy: Cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid. Redox Signal. 2012, 16, 1264–1284. [Google Scholar] [CrossRef] [PubMed]
- Lisanti, M.P.; Martinez-Outschoorn, U.E.; Chiavarina, B.; Pavlides, S.; Whitaker-Menezes, D.; Tsirigos, A.; Witkiewicz, A.; Lin, Z.; Balliet, R.; Howell, A.; et al. Understanding the "lethal" drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol. Ther. 2010, 10, 537–542. [Google Scholar] [CrossRef] [PubMed]
- Martinez-Outschoorn, U.E.; Trimmer, C.; Lin, Z.; Whitaker-Menezes, D.; Chiavarina, B.; Zhou, J.; Wang, C.; Pavlides, S.; Martinez-Cantarin, M.P.; Capozza, F.; et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NF-κB activation in the tumor stromal microenvironment. Cell Cycle 2010, 9, 3515–3533. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Cardena, G.; Martasek, P.; Masters, B.S.; Skidd, P.M.; Couet, J.; Li, S.; Lisanti, M.P.; Sessa, W.C. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J. Biol. Chem. 1997, 272, 25437–25440. [Google Scholar] [CrossRef] [PubMed]
- Whitaker-Menezes, D.; Martinez-Outschoorn, U.E.; Lin, Z.; Ertel, A.; Flomenberg, N.; Witkiewicz, A.K.; Birbe, R.C.; Howell, A.; Pavlides, S.; Gandara, R.; et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011, 10, 1772–1783. [Google Scholar] [CrossRef] [PubMed]
- Whitaker-Menezes, D.; Martinez-Outschoorn, U.E.; Flomenberg, N.; Birbe, R.C.; Witkiewicz, A.K.; Howell, A.; Pavlides, S.; Tsirigos, A.; Ertel, A.; Pestell, R.G.; et al. Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: Visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle 2011, 10, 4047–4064. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Regina, A.; Jodoin, J.; Khoueir, P.; Rolland, Y.; Berthelet, F.; Moumdjian, R.; Fenart, L.; Cecchelli, R.; Demeule, M.; Beliveau, R. Down-regulation of caveolin-1 in glioma vasculature: Modulation by radiotherapy. J. Neurosci. Res. 2004, 75, 291–299. [Google Scholar] [CrossRef] [PubMed]
- Miranda-Goncalves, V.; Honavar, M.; Pinheiro, C.; Martinho, O.; Pires, M.M.; Pinheiro, C.; Cordeiro, M.; Bebiano, G.; Costa, P.; Palmeirim, I.; et al. Monocarboxylate transporters (MCTs) in gliomas: Expression and exploitation as therapeutic targets. Neuro-Oncology 2013, 15, 172–188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Debnath, J. Detachment-induced autophagy during anoikis and lumen formation in epithelial acini. Autophagy 2008, 4, 351–353. [Google Scholar] [CrossRef] [PubMed]
- Avivar-Valderas, A.; Salas, E.; Bobrovnikova-Marjon, E.; Diehl, J.A.; Nagi, C.; Debnath, J.; Aguirre-Ghiso, J.A. PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol. Cell. Biol. 2011, 31, 3616–3629. [Google Scholar] [CrossRef] [PubMed]
- Dey, S.; Sayers, C.M.; Verginadis, I.I.; Lehman, S.L.; Cheng, Y.; Cerniglia, G.J.; Tuttle, S.W.; Feldman, M.D.; Zhang, P.J.; Fuchs, S.Y.; et al. ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J. Clin. Investig. 2015, 125, 2592–2608. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fung, C.; Lock, R.; Gao, S.; Salas, E.; Debnath, J. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol. Biol. Cell 2008, 19, 797–806. [Google Scholar] [CrossRef] [PubMed]
- Lum, J.J.; Bauer, D.E.; Kong, M.; Harris, M.H.; Li, C.; Lindsten, T.; Thompson, C.B. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005, 120, 237–248. [Google Scholar] [CrossRef] [PubMed]
- Vial, D.; McKeown-Longo, P.J. Role of EGFR expression levels in the regulation of integrin function by EGF. Mol. Carcinogen. 2016, 55, 1118–1123. [Google Scholar] [CrossRef] [PubMed]
- Peart, T.; Ramos Valdes, Y.; Correa, R.J.; Fazio, E.; Bertrand, M.; McGee, J.; Prefontaine, M.; Sugimoto, A.; DiMattia, G.E.; Shepherd, T.G. Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids. Oncotarget 2015, 6, 22424–22438. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Magnus, N.; Garnier, D.; Meehan, B.; McGraw, S.; Lee, T.H.; Caron, M.; Bourque, G.; Milsom, C.; Jabado, N.; Trasler, J.; et al. Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations. Proc. Natl. Acad. Sci. USA 2014, 111, 3544–3549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Magnus, N.; Garnier, D.; Rak, J. Oncogenic epidermal growth factor receptor up-regulates multiple elements of the tissue factor signaling pathway in human glioma cells. Blood 2010, 116, 815–818. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanzawa, T.; Germano, I.M.; Komata, T.; Ito, H.; Kondo, Y.; Kondo, S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004, 11, 448–457. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ito, H.; Daido, S.; Kanzawa, T.; Kondo, S.; Kondo, Y. Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int. J. Oncol. 2005, 26, 1401–1410. [Google Scholar] [CrossRef] [PubMed]
- Gump, J.M.; Thorburn, A. Autophagy and apoptosis: What is the connection? Trends Cell Biol. 2011, 21, 387–392. [Google Scholar] [CrossRef] [PubMed]
- Pattingre, S.; Tassa, A.; Qu, X.; Garuti, R.; Liang, X.H.; Mizushima, N.; Packer, M.; Schneider, M.D.; Levine, B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005, 122, 927–939. [Google Scholar] [CrossRef] [PubMed]
- Luo, S.; Rubinsztein, D.C. Apoptosis blocks Beclin 1-dependent autophagosome synthesis: An effect rescued by Bcl-xL. Cell Death Differ. 2010, 17, 268–277. [Google Scholar] [CrossRef] [PubMed]
- Wei, Y.; Pattingre, S.; Sinha, S.; Bassik, M.; Levine, B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell 2008, 30, 678–688. [Google Scholar] [CrossRef] [PubMed]
- Levin-Salomon, V.; Bialik, S.; Kimchi, A. DAP-kinase and autophagy. Apoptosis 2014, 19, 346–356. [Google Scholar] [CrossRef] [PubMed]
- Mukhopadhyay, S.; Panda, P.K.; Sinha, N.; Das, D.N.; Bhutia, S.K. Autophagy and apoptosis: Where do they meet? Apoptosis 2014, 19, 555–566. [Google Scholar] [CrossRef] [PubMed]
- Rubinstein, A.D.; Eisenstein, M.; Ber, Y.; Bialik, S.; Kimchi, A. The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to promote mitochondrial apoptosis. Mol. Cell 2011, 44, 698–709. [Google Scholar] [CrossRef] [PubMed]
- Strappazzon, F.; Vietri-Rudan, M.; Campello, S.; Nazio, F.; Florenzano, F.; Fimia, G.M.; Piacentini, M.; Levine, B.; Cecconi, F. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J. 2011, 30, 1195–1208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ojha, R.; Ishaq, M.; Singh, S.K. Caspase-mediated crosstalk between autophagy and apoptosis: Mutual adjustment or matter of dominance. J. Cancer Res. Ther. 2015, 11, 514–524. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Zhao, L.; Liu, L.; Gao, P.; Tian, W.; Wang, X.; Jin, H.; Xu, H.; Chen, Q. Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis. Protein Cell 2010, 1, 468–477. [Google Scholar] [CrossRef] [PubMed]
- Betin, V.M.; Lane, J.D. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J. Cell Sci. 2009, 122, 2554–2566. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pagliarini, V.; Wirawan, E.; Romagnoli, A.; Ciccosanti, F.; Lisi, G.; Lippens, S.; Cecconi, F.; Fimia, G.M.; Vandenabeele, P.; Corazzari, M.; et al. Proteolysis of Ambra1 during apoptosis has a role in the inhibition of the autophagic pro-survival response. Cell Death Differ. 2012, 19, 1495–1504. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pankiv, S.; Clausen, T.H.; Lamark, T.; Brech, A.; Bruun, J.A.; Outzen, H.; Overvatn, A.; Bjorkoy, G.; Johansen, T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 2007, 282, 24131–24145. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.B.; Zhao, W.; Zeng, R.X. Autophagic degradation of caspase-8 protects U87MG cells against H2O2-induced oxidative stress. APJCP 2013, 14, 4095–4099. [Google Scholar] [CrossRef] [PubMed]
- Yin, X.; Cao, L.; Kang, R.; Yang, M.; Wang, Z.; Peng, Y.; Tan, Y.; Liu, L.; Xie, M.; Zhao, Y.; et al. UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation. EMBO Rep. 2011, 12, 727–734. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, G.; Yuan, Y.; Long, M.; Luo, T.; Bian, J.; Liu, X.; Gu, J.; Zou, H.; Song, R.; Wang, Y.; et al. Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture. Sci. Rep. 2017, 7, 977. [Google Scholar] [CrossRef] [PubMed]
- Han, J.; Hou, W.; Goldstein, L.A.; Lu, C.; Stolz, D.B.; Yin, X.M.; Rabinowich, H. Involvement of protective autophagy in TRAIL resistance of apoptosis-defective tumor cells. J. Biol. Chem. 2008, 283, 19665–19677. [Google Scholar] [CrossRef] [PubMed]
- Thorburn, J.; Moore, F.; Rao, A.; Barclay, W.W.; Thomas, L.R.; Grant, K.W.; Cramer, S.D.; Thorburn, A. Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol. Biol. Cell 2005, 16, 1189–1199. [Google Scholar] [CrossRef] [PubMed]
- Herrero-Martin, G.; Hoyer-Hansen, M.; Garcia-Garcia, C.; Fumarola, C.; Farkas, T.; Lopez-Rivas, A.; Jaattela, M. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J. 2009, 28, 677–685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, K.J.; Lee, S.H.; Kim, T.I.; Lee, H.W.; Lee, C.H.; Kim, E.H.; Jang, J.Y.; Choi, K.S.; Kwon, M.H.; Kim, Y.S. A human scFv antibody against TRAIL receptor 2 induces autophagic cell death in both TRAIL-sensitive and TRAIL-resistant cancer cells. Cancer Res. 2007, 67, 7327–7334. [Google Scholar] [CrossRef] [PubMed]
- Vazquez, A.; Bond, E.E.; Levine, A.J.; Bond, G.L. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat. Rev. Drug Discov. 2008, 7, 979–987. [Google Scholar] [CrossRef] [PubMed]
- Takahashi, M.; Kakudo, Y.; Takahashi, S.; Sakamoto, Y.; Kato, S.; Ishioka, C. Overexpression of DRAM enhances p53-dependent apoptosis. Cancer Med. 2013, 2, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Laforge, M.; Limou, S.; Harper, F.; Casartelli, N.; Rodrigues, V.; Silvestre, R.; Haloui, H.; Zagury, J.F.; Senik, A.; Estaquier, J. DRAM triggers lysosomal membrane permeabilization and cell death in CD4(+) T cells infected with HIV. PLoS Pathog. 2013, 9, e1003328. [Google Scholar] [CrossRef] [PubMed]
- Liu, K.; Shi, Y.; Guo, X.H.; Ouyang, Y.B.; Wang, S.S.; Liu, D.J.; Wang, A.N.; Li, N.; Chen, D.X. Phosphorylated AKT inhibits the apoptosis induced by DRAM-mediated mitophagy in hepatocellular carcinoma by preventing the translocation of DRAM to mitochondria. Cell Death Dis. 2014, 5, e1078. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.D.; Qi, L.; Wu, J.C.; Qin, Z.H. DRAM1 regulates autophagy flux through lysosomes. PLoS ONE 2013, 8, e63245. [Google Scholar] [CrossRef] [PubMed]
- Feng, Z.; Hu, W.; de Stanchina, E.; Teresky, A.K.; Jin, S.; Lowe, S.; Levine, A.J. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 2007, 67, 3043–3053. [Google Scholar] [CrossRef] [PubMed]
- Karuman, P.; Gozani, O.; Odze, R.D.; Zhou, X.C.; Zhu, H.; Shaw, R.; Brien, T.P.; Bozzuto, C.D.; Ooi, D.; Cantley, L.C.; et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol. Cell 2001, 7, 1307–1319. [Google Scholar] [CrossRef]
- Gao, W.; Shen, Z.; Shang, L.; Wang, X. Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death. Cell Death Differ. 2011, 18, 1598–1607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brunet, A.; Bonni, A.; Zigmond, M.J.; Lin, M.Z.; Juo, P.; Hu, L.S.; Anderson, M.J.; Arden, K.C.; Blenis, J.; Greenberg, M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999, 96, 857–868. [Google Scholar] [CrossRef]
- Jones, R.G.; Plas, D.R.; Kubek, S.; Buzzai, M.; Mu, J.; Xu, Y.; Birnbaum, M.J.; Thompson, C.B. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 2005, 18, 283–293. [Google Scholar] [CrossRef] [PubMed]
- Kong, M.; Fox, C.J.; Mu, J.; Solt, L.; Xu, A.; Cinalli, R.M.; Birnbaum, M.J.; Lindsten, T.; Thompson, C.B. The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis. Science 2004, 306, 695–698. [Google Scholar] [CrossRef] [PubMed]
- Ro, S.H.; Semple, I.A.; Park, H.; Park, H.; Park, H.W.; Kim, M.; Kim, J.S.; Lee, J.H. Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. FEBS J. 2014, 281, 3816–3827. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tasdemir, E.; Maiuri, M.C.; Galluzzi, L.; Vitale, I.; Djavaheri-Mergny, M.; D’Amelio, M.; Criollo, A.; Morselli, E.; Zhu, C.; Harper, F.; et al. Regulation of autophagy by cytoplasmic p53. Nat. Cell Biol. 2008, 10, 676–687. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morselli, E.; Tasdemir, E.; Maiuri, M.C.; Galluzzi, L.; Kepp, O.; Criollo, A.; Vicencio, J.M.; Soussi, T.; Kroemer, G. Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle 2008, 7, 3056–3061. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef] [PubMed]
- Hegi, M.E.; Diserens, A.C.; Gorlia, T.; Hamou, M.F.; de Tribolet, N.; Weller, M.; Kros, J.M.; Hainfellner, J.A.; Mason, W.; Mariani, L.; et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 2005, 352, 997–1003. [Google Scholar] [CrossRef] [PubMed]
- Carmo, A.; Carvalheiro, H.; Crespo, I.; Nunes, I.; Lopes, M.C. Effect of temozolomide on the U-118 glioma cell line. Oncol. Lett. 2011, 2, 1165–1170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Salvo, M.; Maresca, G.; D’Agnano, I.; Marchese, R.; Stigliano, A.; Gagliassi, R.; Brunetti, E.; Raza, G.H.; De Paula, U.; Bucci, B. Temozolomide induced c-Myc-mediated apoptosis via Akt signalling in MGMT expressing glioblastoma cells. Int. J. Radiat. Biol. 2011, 87, 518–533. [Google Scholar] [CrossRef] [PubMed]
- Wurstle, S.; Schneider, F.; Ringel, F.; Gempt, J.; Lammer, F.; Delbridge, C.; Wu, W.; Schlegel, J. Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner. Oncol. Lett. 2017, 14, 322–328. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, X.Y.; Zhang, L.; Wu, J.; Zhou, L.; Ren, Y.J.; Yang, W.Q.; Ming, Z.J.; Chen, B.; Wang, J.; Zhang, Y.; et al. Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma. PLoS ONE 2013, 8, e81345. [Google Scholar] [CrossRef] [PubMed]
- Roos, W.P.; Batista, L.F.; Naumann, S.C.; Wick, W.; Weller, M.; Menck, C.F.; Kaina, B. Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine. Oncogene 2007, 26, 186–197. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.B.; Wang, Z.; Shu, F.; Jin, Y.H.; Liu, H.Y.; Wang, Q.J.; Yang, Y. Activation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition. J. Biol. Chem. 2010, 285, 40461–40471. [Google Scholar] [CrossRef] [PubMed]
- Ramis, G.; Thomas-Moya, E.; Fernandez de Mattos, S.; Rodriguez, J.; Villalonga, P. EGFR inhibition in glioma cells modulates Rho signaling to inhibit cell motility and invasion and cooperates with temozolomide to reduce cell growth. PLoS ONE 2012, 7, e38770. [Google Scholar] [CrossRef] [PubMed]
- Goodwin, C.R.; Rath, P.; Oyinlade, O.; Lopez, H.; Mughal, S.; Xia, S.; Li, Y.; Kaur, H.; Zhou, X.; Ahmed, A.K.; et al. Crizotinib and erlotinib inhibits growth of c-Met(+)/EGFRvIII(+) primary human glioblastoma xenografts. Clin. Neurol. Neurosurg. 2018, 171, 26–33. [Google Scholar] [CrossRef] [PubMed]
- Karpel-Massler, G.; Westhoff, M.A.; Kast, R.E.; Dwucet, A.; Karpel-Massler, S.; Nonnenmacher, L.; Siegelin, M.D.; Wirtz, C.R.; Debatin, K.M.; Halatsch, M.E. Simultaneous Interference with HER1/EGFR and RAC1 Signaling Drives Cytostasis and Suppression of Survivin in Human Glioma Cells in Vitro. Neurochem. Res. 2017, 42, 1543–1554. [Google Scholar] [CrossRef] [PubMed]
- Shingu, T.; Holmes, L.; Henry, V.; Wang, Q.; Latha, K.; Gururaj, A.E.; Gibson, L.A.; Doucette, T.; Lang, F.F.; Rao, G.; et al. Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells. J. Trans. Med. 2016, 14, 46. [Google Scholar] [CrossRef] [PubMed]
- Eimer, S.; Belaud-Rotureau, M.A.; Airiau, K.; Jeanneteau, M.; Laharanne, E.; Veron, N.; Vital, A.; Loiseau, H.; Merlio, J.P.; Belloc, F. Autophagy inhibition cooperates with erlotinib to induce glioblastoma cell death. Cancer Biol. Ther. 2011, 11, 1017–1027. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kesavabhotla, K.; Schlaff, C.D.; Shin, B.; Mubita, L.; Kaplan, R.; Tsiouris, A.J.; Pannullo, S.C.; Christos, P.; Lavi, E.; Scheff, R.; et al. Phase I/II study of oral erlotinib for treatment of relapsed/refractory glioblastoma multiforme and anaplastic astrocytoma. J. Exp. Ther. Oncol. 2012, 10, 71–81. [Google Scholar] [PubMed]
- Van den Bent, M.J.; Brandes, A.A.; Rampling, R.; Kouwenhoven, M.C.; Kros, J.M.; Carpentier, A.F.; Clement, P.M.; Frenay, M.; Campone, M.; Baurain, J.F.; et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J. Clin. Oncol. 2009, 27, 1268–1274. [Google Scholar] [CrossRef] [PubMed]
- Raizer, J.J.; Giglio, P.; Hu, J.; Groves, M.; Merrell, R.; Conrad, C.; Phuphanich, S.; Puduvalli, V.K.; Loghin, M.; Paleologos, N.; et al. A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients. J. Neuro-Oncol. 2016, 126, 185–192. [Google Scholar] [CrossRef] [PubMed]
- Clarke, J.L.; Molinaro, A.M.; Phillips, J.J.; Butowski, N.A.; Chang, S.M.; Perry, A.; Costello, J.F.; DeSilva, A.A.; Rabbitt, J.E.; Prados, M.D. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro-Oncology 2014, 16, 984–990. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qaddoumi, I.; Kocak, M.; Pai Panandiker, A.S.; Armstrong, G.T.; Wetmore, C.; Crawford, J.R.; Lin, T.; Boyett, J.M.; Kun, L.E.; Boop, F.A.; et al. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas. Front. Oncol. 2014, 4, 67. [Google Scholar] [CrossRef] [PubMed]
- Wen, P.Y.; Chang, S.M.; Lamborn, K.R.; Kuhn, J.G.; Norden, A.D.; Cloughesy, T.F.; Robins, H.I.; Lieberman, F.S.; Gilbert, M.R.; Mehta, M.P.; et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro-Oncology 2014, 16, 567–578. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Halatsch, M.E.; Low, S.; Mursch, K.; Hielscher, T.; Schmidt, U.; Unterberg, A.; Vougioukas, V.I.; Feuerhake, F. Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation. J. Neurosurg. 2009, 111, 211–218. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.Y.; Shen, C.C.; Su, H.L.; Chen, C.J. Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation. J. Neuro-Oncol. 2011, 105, 507–522. [Google Scholar] [CrossRef] [PubMed]
- Guillamo, J.S.; de Bouard, S.; Valable, S.; Marteau, L.; Leuraud, P.; Marie, Y.; Poupon, M.F.; Parienti, J.J.; Raymond, E.; Peschanski, M. Molecular mechanisms underlying effects of epidermal growth factor receptor inhibition on invasion, proliferation, and angiogenesis in experimental glioma. Clin. Cancer Res. 2009, 15, 3697–3704. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.Y.; Kuan, Y.H.; Ou, Y.C.; Li, J.R.; Wu, C.C.; Pan, P.H.; Chen, W.Y.; Huang, H.Y.; Chen, C.J. Autophagy contributes to gefitinib-induced glioma cell growth inhibition. Exp. Cell Res. 2014, 327, 102–112. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Zhang, Y.; Zhang, L.; Ren, X.; Huber-Keener, K.J.; Liu, X.; Zhou, L.; Liao, J.; Keihack, H.; Yan, L.; et al. MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis. Mol. Cancer Ther. 2012, 11, 154–164. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.Y.; Li, J.R.; Wu, C.C.; Ou, Y.C.; Chen, W.Y.; Kuan, Y.H.; Wang, W.Y.; Chen, C.J. Valproic acid sensitizes human glioma cells to gefitinib-induced autophagy. IUBMB Life 2015, 67, 869–879. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chakravarti, A.; Wang, M.; Robins, H.I.; Lautenschlaeger, T.; Curran, W.J.; Brachman, D.G.; Schultz, C.J.; Choucair, A.; Dolled-Filhart, M.; Christiansen, J.; et al. RTOG 0211: A phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients. Int. J. Radiat. Oncol. Biol. Phys. 2013, 85, 1206–1211. [Google Scholar] [CrossRef] [PubMed]
- Doherty, L.; Gigas, D.C.; Kesari, S.; Drappatz, J.; Kim, R.; Zimmerman, J.; Ostrowsky, L.; Wen, P.Y. Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas. Neurology 2006, 67, 156–158. [Google Scholar] [CrossRef] [PubMed]
- Rich, J.N.; Reardon, D.A.; Peery, T.; Dowell, J.M.; Quinn, J.A.; Penne, K.L.; Wikstrand, C.J.; Van Duyn, L.B.; Dancey, J.E.; McLendon, R.E.; et al. Phase II trial of gefitinib in recurrent glioblastoma. J. Clin. Oncol. 2004, 22, 133–142. [Google Scholar] [CrossRef] [PubMed]
- Hegi, M.E.; Diserens, A.C.; Bady, P.; Kamoshima, Y.; Kouwenhoven, M.C.; Delorenzi, M.; Lambiv, W.L.; Hamou, M.F.; Matter, M.S.; Koch, A.; et al. Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib—A phase II trial. Mol. Cancer Ther. 2011, 10, 1102–1112. [Google Scholar] [CrossRef] [PubMed]
- Uhm, J.H.; Ballman, K.V.; Wu, W.; Giannini, C.; Krauss, J.C.; Buckner, J.C.; James, C.D.; Scheithauer, B.W.; Behrens, R.J.; Flynn, P.J.; et al. Phase II evaluation of gefitinib in patients with newly diagnosed Grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074. Int. J. Radiat. Oncol. Biol. Phys. 2011, 80, 347–353. [Google Scholar] [CrossRef] [PubMed]
- Wykosky, J.; Hu, J.; Gomez, G.G.; Taylor, T.; Villa, G.R.; Pizzo, D.; VandenBerg, S.R.; Thorne, A.H.; Chen, C.C.; Mischel, P.S.; et al. A urokinase receptor-Bim signaling axis emerges during EGFR inhibitor resistance in mutant EGFR glioblastoma. Cancer Res. 2015, 75, 394–404. [Google Scholar] [CrossRef] [PubMed]
- Ranza, E.; Mazzini, G.; Facoetti, A.; Nano, R. In-vitro effects of the tyrosine kinase inhibitor imatinib on glioblastoma cell proliferation. J. Neuro-Oncol. 2010, 96, 349–357. [Google Scholar] [CrossRef] [PubMed]
- Kilic, T.; Alberta, J.A.; Zdunek, P.R.; Acar, M.; Iannarelli, P.; O’Reilly, T.; Buchdunger, E.; Black, P.M.; Stiles, C.D. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res. 2000, 60, 5143–5150. [Google Scholar] [PubMed]
- Yang, L.; Xu, Z.Y.; Chen, X.H.; Wang, K.W.; Li, G.F.; Chen, Z.L. Effect of imatinib at different concentrations on rat C6 glioma cell apoptosis and cell cycle. J. South. Med. Univ. 2010, 30, 1089–1091. [Google Scholar]
- Shingu, T.; Fujiwara, K.; Bogler, O.; Akiyama, Y.; Moritake, K.; Shinojima, N.; Tamada, Y.; Yokoyama, T.; Kondo, S. Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity in human malignant glioma cells. Int. J. Cancer 2009, 124, 1060–1071. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bilir, A.; Erguven, M.; Oktem, G.; Ozdemir, A.; Uslu, A.; Aktas, E.; Bonavida, B. Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma. Int. J. Oncol. 2008, 32, 829–839. [Google Scholar] [PubMed]
- Erguven, M.; Yazihan, N.; Aktas, E.; Sabanci, A.; Li, C.J.; Oktem, G.; Bilir, A. Carvedilol in glioma treatment alone and with imatinib in vitro. Int. J. Oncol. 2010, 36, 857–866. [Google Scholar] [CrossRef] [PubMed]
- Reardon, D.A.; Desjardins, A.; Vredenburgh, J.J.; Sathornsumetee, S.; Rich, J.N.; Quinn, J.A.; Lagattuta, T.F.; Egorin, M.J.; Gururangan, S.; McLendon, R.; et al. Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: Phase 1 trial in adults with malignant glioma. Neuro-Oncology 2008, 10, 330–340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wen, P.Y.; Yung, W.K.; Lamborn, K.R.; Dahia, P.L.; Wang, Y.; Peng, B.; Abrey, L.E.; Raizer, J.; Cloughesy, T.F.; Fink, K.; et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin. Cancer Res. 2006, 12, 4899–4907. [Google Scholar] [CrossRef] [PubMed]
- Leis, J.F.; Stepan, D.E.; Curtin, P.T.; Ford, J.M.; Peng, B.; Schubach, S.; Druker, B.J.; Maziarz, R.T. Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571). Leuk. Lymphoma 2004, 45, 695–698. [Google Scholar] [CrossRef] [PubMed]
- Le Coutre, P.; Kreuzer, K.A.; Pursche, S.; Bonin, M.; Leopold, T.; Baskaynak, G.; Dorken, B.; Ehninger, G.; Ottmann, O.; Jenke, A.; et al. Pharmacokinetics and cellular uptake of imatinib and its main metabolite CGP74588. Cancer Chemother. Pharmacol. 2004, 53, 313–323. [Google Scholar] [CrossRef] [PubMed]
- Neville, K.; Parise, R.A.; Thompson, P.; Aleksic, A.; Egorin, M.J.; Balis, F.M.; McGuffey, L.; McCully, C.; Berg, S.L.; Blaney, S.M. Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to nonhuman primates. Clin. Cancer Res. 2004, 10, 2525–2529. [Google Scholar] [CrossRef] [PubMed]
- Razis, E.; Selviaridis, P.; Labropoulos, S.; Norris, J.L.; Zhu, M.J.; Song, D.D.; Kalebic, T.; Torrens, M.; Kalogera-Fountzila, A.; Karkavelas, G.; et al. Phase II study of neoadjuvant imatinib in glioblastoma: Evaluation of clinical and molecular effects of the treatment. Clin. Cancer Res. 2009, 15, 6258–6266. [Google Scholar] [CrossRef] [PubMed]
- Paulsson, J.; Lindh, M.B.; Jarvius, M.; Puputti, M.; Nister, M.; Nupponen, N.N.; Paulus, W.; Soderberg, O.; Dresemann, G.; von Deimling, A.; et al. Prognostic but not predictive role of platelet-derived growth factor receptors in patients with recurrent glioblastoma. Int. J. Cancer 2011, 128, 1981–1988. [Google Scholar] [CrossRef] [PubMed]
- Frolov, A.; Evans, I.M.; Li, N.; Sidlauskas, K.; Paliashvili, K.; Lockwood, N.; Barrett, A.; Brandner, S.; Zachary, I.C.; Frankel, P. Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling. Sci. Rep. 2016, 6, 27378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moeckel, S.; Meyer, K.; Leukel, P.; Heudorfer, F.; Seliger, C.; Stangl, C.; Bogdahn, U.; Proescholdt, M.; Brawanski, A.; Vollmann-Zwerenz, A.; et al. Response-predictive gene expression profiling of glioma progenitor cells in vitro. PLoS ONE 2014, 9, e108632. [Google Scholar] [CrossRef] [PubMed]
- De Bouard, S.; Herlin, P.; Christensen, J.G.; Lemoisson, E.; Gauduchon, P.; Raymond, E.; Guillamo, J.S. Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro-Oncology 2007, 9, 412–423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abdel-Aziz, A.K.; Shouman, S.; El-Demerdash, E.; Elgendy, M.; Abdel-Naim, A.B. Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries. Chem.-Biol. Interact. 2014, 217, 28–40. [Google Scholar] [CrossRef] [PubMed]
- Joshi, A.D.; Loilome, W.; Siu, I.M.; Tyler, B.; Gallia, G.L.; Riggins, G.J. Evaluation of tyrosine kinase inhibitor combinations for glioblastoma therapy. PLoS ONE 2012, 7, e44372. [Google Scholar] [CrossRef] [PubMed]
- Czabanka, M.; Bruenner, J.; Parmaksiz, G.; Broggini, T.; Topalovic, M.; Bayerl, S.H.; Auf, G.; Kremenetskaia, I.; Nieminen, M.; Jabouille, A.; et al. Combined temozolomide and sunitinib treatment leads to better tumour control but increased vascular resistance in O6-methylguanine methyltransferase-methylated gliomas. Eur. J. Cancer 2013, 49, 2243–2252. [Google Scholar] [CrossRef] [PubMed]
- Reardon, D.A.; Vredenburgh, J.J.; Coan, A.; Desjardins, A.; Peters, K.B.; Gururangan, S.; Sathornsumetee, S.; Rich, J.N.; Herndon, J.E.; Friedman, H.S. Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma. J. Neuro-Oncol. 2011, 105, 621–627. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kreisl, T.N.; Smith, P.; Sul, J.; Salgado, C.; Iwamoto, F.M.; Shih, J.H.; Fine, H.A. Continuous daily sunitinib for recurrent glioblastoma. J. Neuro-Oncol. 2013, 111, 41–48. [Google Scholar] [CrossRef] [PubMed]
- Balana, C.; Gil, M.J.; Perez, P.; Reynes, G.; Gallego, O.; Ribalta, T.; Capellades, J.; Gonzalez, S.; Verger, E. Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: Results of a phase II study. Target. Oncol. 2014, 9, 321–329. [Google Scholar] [CrossRef] [PubMed]
- Oberoi, R.K.; Mittapalli, R.K.; Elmquist, W.F. Pharmacokinetic assessment of efflux transport in sunitinib distribution to the brain. J. Pharmacol. Exp. Ther. 2013, 347, 755–764. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Q.; Lv, H.; Mazloom, A.R.; Xu, H.; Ma’ayan, A.; Gallo, J.M. Activation of alternate prosurvival pathways accounts for acquired sunitinib resistance in U87MG glioma xenografts. J. Pharmacol. Exp. Ther. 2012, 343, 509–519. [Google Scholar] [CrossRef] [PubMed]
- Sandstrom, M.; Johansson, M.; Andersson, U.; Bergh, A.; Bergenheim, A.T.; Henriksson, R. The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model. Br. J. Cancer 2004, 91, 1174–1180. [Google Scholar] [CrossRef] [PubMed]
- Yiin, J.J.; Hu, B.; Schornack, P.A.; Sengar, R.S.; Liu, K.W.; Feng, H.; Lieberman, F.S.; Chiou, S.H.; Sarkaria, J.N.; Wiener, E.C.; et al. ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain. Mol. Cancer Ther. 2010, 9, 929–941. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Zheng, H.; Ruan, J.; Fang, W.; Li, A.; Tian, G.; Niu, X.; Luo, S.; Zhao, P. Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma. Br. J. Cancer 2013, 109, 164–171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sandstrom, M.; Johansson, M.; Bergstrom, P.; Bergenheim, A.T.; Henriksson, R. Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model. J. Neuro-Oncol. 2008, 88, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Drappatz, J.; Norden, A.D.; Wong, E.T.; Doherty, L.M.; Lafrankie, D.C.; Ciampa, A.; Kesari, S.; Sceppa, C.; Gerard, M.; Phan, P.; et al. Phase I study of vandetanib with radiotherapy and temozolomide for newly diagnosed glioblastoma. Int. J. Radiat. Oncol. Biol. Phys. 2010, 78, 85–90. [Google Scholar] [CrossRef] [PubMed]
- Kreisl, T.N.; McNeill, K.A.; Sul, J.; Iwamoto, F.M.; Shih, J.; Fine, H.A. A phase I/II trial of vandetanib for patients with recurrent malignant glioma. Neuro-Oncology 2012, 14, 1519–1526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, E.Q.; Kaley, T.J.; Duda, D.G.; Schiff, D.; Lassman, A.B.; Wong, E.T.; Mikkelsen, T.; Purow, B.W.; Muzikansky, A.; Ancukiewicz, M.; et al. A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients. Clin. Cancer Res. 2015, 21, 3610–3618. [Google Scholar] [CrossRef] [PubMed]
- Pham, K.; Luo, D.; Siemann, D.W.; Law, B.K.; Reynolds, B.A.; Hothi, P.; Foltz, G.; Harrison, J.K. VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFbetaR signaling-dependent manner. Cancer Lett. 2015, 360, 60–67. [Google Scholar] [CrossRef] [PubMed]
- Arbab, A.S. Activation of alternative pathways of angiogenesis and involvement of stem cells following anti-angiogenesis treatment in glioma. Histol. Histopathol. 2012, 27, 549–557. [Google Scholar] [CrossRef] [PubMed]
- Delmas, C.; End, D.; Rochaix, P.; Favre, G.; Toulas, C.; Cohen-Jonathan, E. The farnesyltransferase inhibitor R115777 reduces hypoxia and matrix metalloproteinase 2 expression in human glioma xenograft. Clin. Cancer Res. 2003, 9, 6062–6068. [Google Scholar] [PubMed]
- Wang, C.C.; Liao, Y.P.; Mischel, P.S.; Iwamoto, K.S.; Cacalano, N.A.; McBride, W.H. HDJ-2 as a target for radiosensitization of glioblastoma multiforme cells by the farnesyltransferase inhibitor R115777 and the role of the p53/p21 pathway. Cancer Res. 2006, 66, 6756–6762. [Google Scholar] [CrossRef] [PubMed]
- Cloughesy, T.F.; Kuhn, J.; Robins, H.I.; Abrey, L.; Wen, P.; Fink, K.; Lieberman, F.S.; Mehta, M.; Chang, S.; Yung, A.; et al. Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. J. Clin. Oncol. 2005, 23, 6647–6656. [Google Scholar] [CrossRef] [PubMed]
- Lustig, R.; Mikkelsen, T.; Lesser, G.; Grossman, S.; Ye, X.; Desideri, S.; Fisher, J.; Wright, J.; New Approaches to Brain Tumor Therapy, C.N.S.C. Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease. Neuro-Oncology 2008, 10, 1004–1009. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ducassou, A.; Uro-Coste, E.; Verrelle, P.; Filleron, T.; Benouaich-Amiel, A.; Lubrano, V.; Sol, J.C.; Delisle, M.B.; Favre, G.; Ken, S.; et al. alphavbeta3 Integrin and Fibroblast growth factor receptor 1 (FGFR1): Prognostic factors in a phase I-II clinical trial associating continuous administration of Tipifarnib with radiotherapy for patients with newly diagnosed glioblastoma. Eur. J. Cancer 2013, 49, 2161–2169. [Google Scholar] [CrossRef] [PubMed]
- Cloughesy, T.F.; Wen, P.Y.; Robins, H.I.; Chang, S.M.; Groves, M.D.; Fink, K.L.; Junck, L.; Schiff, D.; Abrey, L.; Gilbert, M.R.; et al. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. J. Clin. Oncol. 2006, 24, 3651–3656. [Google Scholar] [CrossRef] [PubMed]
- Feldkamp, M.M.; Lau, N.; Roncari, L.; Guha, A. Isotype-specific Ras.GTP-levels predict the efficacy of farnesyl transferase inhibitors against human astrocytomas regardless of Ras mutational status. Cancer Res. 2001, 61, 4425–4431. [Google Scholar] [PubMed]
- Glass, T.L.; Liu, T.J.; Yung, W.K. Inhibition of cell growth in human glioblastoma cell lines by farnesyltransferase inhibitor SCH66336. Neuro-Oncology 2000, 2, 151–158. [Google Scholar] [CrossRef] [PubMed]
- Chaponis, D.; Barnes, J.W.; Dellagatta, J.L.; Kesari, S.; Fast, E.; Sauvageot, C.; Panagrahy, D.; Greene, E.R.; Ramakrishna, N.; Wen, P.Y.; et al. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for orthotopic malignant gliomas. J. Neuro-Oncol. 2011, 104, 179–189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pan, J.; Chen, B.; Su, C.H.; Zhao, R.; Xu, Z.X.; Sun, L.; Lee, M.H.; Yeung, S.C. Autophagy induced by farnesyltransferase inhibitors in cancer cells. Cancer Biol. Ther. 2008, 7, 1679–1684. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yust-Katz, S.; Liu, D.; Yuan, Y.; Liu, V.; Kang, S.; Groves, M.; Puduvalli, V.; Levin, V.; Conrad, C.; Colman, H.; et al. Phase 1/1b study of lonafarnib and temozolomide in patients with recurrent or temozolomide refractory glioblastoma. Cancer 2013, 119, 2747–2753. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, S.M.; Wen, P.; Cloughesy, T.; Greenberg, H.; Schiff, D.; Conrad, C.; Fink, K.; Robins, H.I.; De Angelis, L.; Raizer, J.; et al. Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Investig. New Drugs 2005, 23, 357–361. [Google Scholar] [CrossRef] [PubMed]
- Uhrbom, L.; Nerio, E.; Holland, E.C. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat. Med. 2004, 10, 1257–1260. [Google Scholar] [CrossRef] [PubMed]
- Pitter, K.L.; Galban, C.J.; Galban, S.; Tehrani, O.S.; Li, F.; Charles, N.; Bradbury, M.S.; Becher, O.J.; Chenevert, T.L.; Rehemtulla, A.; et al. Perifosine and CCI 779 co-operate to induce cell death and decrease proliferation in PTEN-intact and PTEN-deficient PDGF-driven murine glioblastoma. PLoS ONE 2011, 6, e14545. [Google Scholar] [CrossRef]
- Tsoli, M.; Liu, J.; Franshaw, L.; Shen, H.; Cheng, C.; Jung, M.; Joshi, S.; Ehteda, A.; Khan, A.; Montero-Carcabosso, A.; et al. Dual targeting of mitochondrial function and mTOR pathway as a therapeutic strategy for diffuse intrinsic pontine glioma. Oncotarget 2018, 9, 7541–7556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chandrika, G.; Natesh, K.; Ranade, D.; Chugh, A.; Shastry, P. Mammalian target of rapamycin inhibitors, temsirolimus and torin 1, attenuate stemness-associated properties and expression of mesenchymal markers promoted by phorbol-myristate-acetate and oncostatin-M in glioblastoma cells. Tumour Biol. 2017, 39, 1010428317695921. [Google Scholar] [CrossRef] [PubMed]
- Lassen, U.; Sorensen, M.; Gaziel, T.B.; Hasselbalch, B.; Poulsen, H.S. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. AntiCancer Res. 2013, 33, 1657–1660. [Google Scholar] [PubMed]
- Lee, E.Q.; Kuhn, J.; Lamborn, K.R.; Abrey, L.; DeAngelis, L.M.; Lieberman, F.; Robins, H.I.; Chang, S.M.; Yung, W.K.; Drappatz, J.; et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. Neuro-Oncology 2012, 14, 1511–1518. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wick, W.; Gorlia, T.; Bady, P.; Platten, M.; van den Bent, M.J.; Taphoorn, M.J.; Steuve, J.; Brandes, A.A.; Hamou, M.F.; Wick, A.; et al. Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082). Clin. Cancer Res. 2016, 22, 4797–4806. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Josset, E.; Burckel, H.; Noel, G.; Bischoff, P. The mTOR inhibitor RAD001 potentiates autophagic cell death induced by temozolomide in a glioblastoma cell line. AntiCancer Res. 2013, 33, 1845–1851. [Google Scholar] [PubMed]
- Venkatesh, H.S.; Chaumeil, M.M.; Ward, C.S.; Haas-Kogan, D.A.; James, C.D.; Ronen, S.M. Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma. Neuro-Oncology 2012, 14, 315–325. [Google Scholar] [CrossRef] [PubMed]
- Olmez, I.; Brenneman, B.; Xiao, A.; Serbulea, V.; Benamar, M.; Zhang, Y.; Manigat, L.; Abbas, T.; Lee, J.; Nakano, I.; et al. Combined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms. Clin. Cancer Res. 2017, 23, 6958–6968. [Google Scholar] [CrossRef] [PubMed]
- Minocha, M.; Khurana, V.; Qin, B.; Pal, D.; Mitra, A.K. Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors. Int. J. Pharm. 2012, 434, 306–314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goudar, R.K.; Shi, Q.; Hjelmeland, M.D.; Keir, S.T.; McLendon, R.E.; Wikstrand, C.J.; Reese, E.D.; Conrad, C.A.; Traxler, P.; Lane, H.A.; et al. Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol. Cancer Ther. 2005, 4, 101–112. [Google Scholar] [PubMed]
- Alonso, M.M.; Jiang, H.; Yokoyama, T.; Xu, J.; Bekele, N.B.; Lang, F.F.; Kondo, S.; Gomez-Manzano, C.; Fueyo, J. Delta-24-RGD in combination with RAD001 induces enhanced anti-glioma effect via autophagic cell death. Mol. Ther. 2008, 16, 487–493. [Google Scholar] [CrossRef] [PubMed]
- Chinnaiyan, P.; Won, M.; Wen, P.Y.; Rojiani, A.M.; Wendland, M.; Dipetrillo, T.A.; Corn, B.W.; Mehta, M.P. RTOG 0913: A phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Int. J. Radiat. Oncol. Biol. Phys. 2013, 86, 880–884. [Google Scholar] [CrossRef] [PubMed]
- Hainsworth, J.D.; Shih, K.C.; Shepard, G.C.; Tillinghast, G.W.; Brinker, B.T.; Spigel, D.R. Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin. Adv. Hematol. Oncol. 2012, 10, 240–246. [Google Scholar] [PubMed]
- Kreisl, T.N.; Lassman, A.B.; Mischel, P.S.; Rosen, N.; Scher, H.I.; Teruya-Feldstein, J.; Shaffer, D.; Lis, E.; Abrey, L.E. A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM). J. Neuro-Oncol. 2009, 92, 99–105. [Google Scholar] [CrossRef] [PubMed]
- Arcella, A.; Biagioni, F.; Antonietta Oliva, M.; Bucci, D.; Frati, A.; Esposito, V.; Cantore, G.; Giangaspero, F.; Fornai, F. Rapamycin inhibits the growth of glioblastoma. Brain Res. 2013, 1495, 37–51. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.Y.; Lu, K.V.; Zhu, S.; Dia, E.Q.; Vivanco, I.; Shackleford, G.M.; Cavenee, W.K.; Mellinghoff, I.K.; Cloughesy, T.F.; Sawyers, C.L.; et al. Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells. Cancer Res. 2006, 66, 7864–7869. [Google Scholar] [CrossRef] [PubMed]
- Iwamaru, A.; Kondo, Y.; Iwado, E.; Aoki, H.; Fujiwara, K.; Yokoyama, T.; Mills, G.B.; Kondo, S. Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells. Oncogene 2007, 26, 1840–1851. [Google Scholar] [CrossRef] [PubMed]
- Takeuchi, H.; Kondo, Y.; Fujiwara, K.; Kanzawa, T.; Aoki, H.; Mills, G.B.; Kondo, S. Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res. 2005, 65, 3336–3346. [Google Scholar] [CrossRef] [PubMed]
- Zhuang, W.Z.; Long, L.M.; Ji, W.J.; Liang, Z.Q. Rapamycin induces differentiation of glioma stem/progenitor cells by activating autophagy. Chin. J. Cancer 2011, 30, 712–720. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yokoyama, T.; Iwado, E.; Kondo, Y.; Aoki, H.; Hayashi, Y.; Georgescu, M.M.; Sawaya, R.; Hess, K.R.; Mills, G.B.; Kawamura, H.; et al. Autophagy-inducing agents augment the antitumor effect of telerase-selve oncolytic adenovirus OBP-405 on glioblastoma cells. Gene Ther. 2008, 15, 1233–1239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nam, H.Y.; Han, M.W.; Chang, H.W.; Lee, Y.S.; Lee, M.; Lee, H.J.; Lee, B.W.; Lee, H.J.; Lee, K.E.; Jung, M.K.; et al. Radioresistant cancer cells can be conditioned to enter senescence by mTOR inhibition. Cancer Res. 2013, 73, 4267–4277. [Google Scholar] [CrossRef] [PubMed]
- Hsu, S.P.C.; Kuo, J.S.; Chiang, H.C.; Wang, H.E.; Wang, Y.S.; Huang, C.C.; Huang, Y.C.; Chi, M.S.; Mehta, M.P.; Chi, K.H. Temozolomide, sirolimus and chloroquine is a new therapeutic combination that synergizes to disrupt lysosomal function and cholesterol homeostasis in GBM cells. Oncotarget 2018, 9, 6883–6896. [Google Scholar] [CrossRef] [PubMed]
- Reardon, D.A.; Desjardins, A.; Vredenburgh, J.J.; Gururangan, S.; Friedman, A.H.; Herndon, J.E., 2nd; Marcello, J.; Norfleet, J.A.; McLendon, R.E.; Sampson, J.H.; et al. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J. Neuro-Oncol. 2010, 96, 219–230. [Google Scholar] [CrossRef] [PubMed]
- Chheda, M.G.; Wen, P.Y.; Hochberg, F.H.; Chi, A.S.; Drappatz, J.; Eichler, A.F.; Yang, D.; Beroukhim, R.; Norden, A.D.; Gerstner, E.R.; et al. Vandetanib plus sirolimus in adults with recurrent glioblastoma: Results of a phase I and dose expansion cohort study. J. Neuro-Oncol. 2015, 121, 627–634. [Google Scholar] [CrossRef] [PubMed]
- O’Reilly, K.E.; Rojo, F.; She, Q.B.; Solit, D.; Mills, G.B.; Smith, D.; Lane, H.; Hofmann, F.; Hicklin, D.J.; Ludwig, D.L.; et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006, 66, 1500–1508. [Google Scholar] [CrossRef] [PubMed]
- Hockenbery, D.; Nunez, G.; Milliman, C.; Schreiber, R.D.; Korsmeyer, S.J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990, 348, 334–336. [Google Scholar] [CrossRef] [PubMed]
- Tagscherer, K.E.; Fassl, A.; Campos, B.; Farhadi, M.; Kraemer, A.; Bock, B.C.; Macher-Goeppinger, S.; Radlwimmer, B.; Wiestler, O.D.; Herold-Mende, C.; et al. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene 2008, 27, 6646–6656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oltersdorf, T.; Elmore, S.W.; Shoemaker, A.R.; Armstrong, R.C.; Augeri, D.J.; Belli, B.A.; Bruncko, M.; Deckwerth, T.L.; Dinges, J.; Hajduk, P.J.; et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005, 435, 677–681. [Google Scholar] [CrossRef] [PubMed]
- Premkumar, D.R.; Jane, E.P.; Pollack, I.F. Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells. Cancer Biol. Ther. 2015, 16, 233–243. [Google Scholar] [CrossRef] [PubMed]
- Jane, E.P.; Premkumar, D.R.; Cavaleri, J.M.; Sutera, P.A.; Rajasekar, T.; Pollack, I.F. Dinaciclib, a Cyclin-Dependent Kinase Inhibitor Promotes Proteasomal Degradation of Mcl-1 and Enhances ABT-737-Mediated Cell Death in Malignant Human Glioma Cell Lines. J. Pharmacol. Exp. Ther. 2016, 356, 354–365. [Google Scholar] [CrossRef] [PubMed]
- Kiprianova, I.; Remy, J.; Milosch, N.; Mohrenz, I.V.; Seifert, V.; Aigner, A.; Kogel, D. Sorafenib Sensitizes Glioma Cells to the BH3 Mimetic ABT-737 by Targeting MCL1 in a STAT3-Dependent Manner. Neoplasia 2015, 17, 564–573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jane, E.P.; Premkumar, D.R.; DiDomenico, J.D.; Hu, B.; Cheng, S.Y.; Pollack, I.F. YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context. Mol. Cancer Ther. 2013, 12, 326–338. [Google Scholar] [CrossRef] [PubMed]
- Cristofanon, S.; Fulda, S. ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells. Cell Death Dis. 2012, 3, e432. [Google Scholar] [CrossRef] [PubMed]
- Gratas, C.; Sery, Q.; Rabe, M.; Oliver, L.; Vallette, F.M. Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma. Oncotarget 2014, 5, 2428–2435. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, M.C.; Loh, J.K.; Li, Y.Y.; Huang, W.S.; Chou, C.H.; Cheng, J.T.; Wang, Y.T.; Lieu, A.S.; Howng, S.L.; Hong, Y.R.; et al. Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy: A prospective combination of ABT-737 and TMZ for treating glioma. Int. J. Oncol. 2015, 46, 1304–1316. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Voss, V.; Senft, C.; Lang, V.; Ronellenfitsch, M.W.; Steinbach, J.P.; Seifert, V.; Kogel, D. The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. Mol. Cancer Res. 2010, 8, 1002–1016. [Google Scholar] [CrossRef] [PubMed]
- Coyle, T.; Levante, S.; Shetler, M.; Winfield, J. In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines. J. Neuro-Oncol. 1994, 19, 25–35. [Google Scholar] [CrossRef]
- Jang, J.H.; Surh, Y.J. Potentiation of cellular antioxidant capacity by Bcl-2: Implications for its antiapoptotic function. Biochem. Pharmacol. 2003, 66, 1371–1379. [Google Scholar] [CrossRef]
- Antonietti, P.; Linder, B.; Hehlgans, S.; Mildenberger, I.C.; Burger, M.C.; Fulda, S.; Steinbach, J.P.; Gessler, F.; Rodel, F.; Mittelbronn, M.; et al. Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic-Induced Apoptosis. Mol. Cancer Ther. 2017, 16, 156–168. [Google Scholar] [CrossRef] [PubMed]
- Boiani, M.; Daniel, C.; Liu, X.; Hogarty, M.D.; Marnett, L.J. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J. Biol. Chem. 2013, 288, 6980–6990. [Google Scholar] [CrossRef] [PubMed]
- Festa, M.; Del Valle, L.; Khalili, K.; Franco, R.; Scognamiglio, G.; Graziano, V.; De Laurenzi, V.; Turco, M.C.; Rosati, A. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. Am. J. Pathol. 2011, 178, 2504–2512. [Google Scholar] [CrossRef] [PubMed]
- Jarzabek, M.A.; Amberger-Murphy, V.; Callanan, J.J.; Gao, C.; Zagozdzon, A.M.; Shiels, L.; Wang, J.; Ligon, K.L.; Rich, B.E.; Dicker, P.; et al. Interrogation of gossypol therapy in glioblastoma implementing cell line and patient-derived tumour models. Br. J. Cancer 2014, 111, 2275–2286. [Google Scholar] [CrossRef] [PubMed]
- Bushunow, P.; Reidenberg, M.M.; Wasenko, J.; Winfield, J.; Lorenzo, B.; Lemke, S.; Himpler, B.; Corona, R.; Coyle, T. Gossypol treatment of recurrent adult malignant gliomas. J. Neuro-Oncol. 1999, 43, 79–86. [Google Scholar] [CrossRef]
- Imanshahidi, M.; Hosseinzadeh, H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother. Res. 2008, 22, 999–1012. [Google Scholar] [CrossRef] [PubMed]
- Eom, K.S.; Kim, H.J.; So, H.S.; Park, R.; Kim, T.Y. Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. Biol. Pharm. Bull. 2010, 33, 1644–1649. [Google Scholar] [CrossRef] [PubMed]
- Eom, K.S.; Hong, J.M.; Youn, M.J.; So, H.S.; Park, R.; Kim, J.M.; Kim, T.Y. Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway. Biol. Pharm. Bull. 2008, 31, 558–562. [Google Scholar] [CrossRef] [PubMed]
- Chen, T.C.; Lai, K.C.; Yang, J.S.; Liao, C.L.; Hsia, T.C.; Chen, G.W.; Lin, J.J.; Lin, H.J.; Chiu, T.H.; Tang, Y.J.; et al. Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells. Int. J. Oncol. 2009, 34, 1681–1690. [Google Scholar] [PubMed]
- Lin, T.H.; Kuo, H.C.; Chou, F.P.; Lu, F.J. Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide. BMC Cancer 2008, 8, 58. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Qi, Q.; Feng, Z.; Zhang, X.; Huang, B.; Chen, A.; Prestegarden, L.; Li, X.; Wang, J. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway. Oncotarget 2016, 7, 66944–66958. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mariani, S.M.; Krammer, P.H. Differential regulation of TRAIL and CD95 ligand in transformed cells of the T and B lymphocyte lineage. Eur. J. Immunol. 1998, 28, 973–982. [Google Scholar] [CrossRef] [Green Version]
- Ashkenazi, A.; Pai, R.C.; Fong, S.; Leung, S.; Lawrence, D.A.; Marsters, S.A.; Blackie, C.; Chang, L.; McMurtrey, A.E.; Hebert, A.; et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J. Clin. Investig. 1999, 104, 155–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jane, E.P.; Premkumar, D.R.; Pollack, I.F. Bortezomib sensitizes malignant human glioma cells to TRAIL, mediated by inhibition of the NF-κB signaling pathway. Mol. Cancer Ther. 2011, 10, 198–208. [Google Scholar] [CrossRef] [PubMed]
- Guo, L.; Fan, L.; Pang, Z.; Ren, J.; Ren, Y.; Li, J.; Chen, J.; Wen, Z.; Jiang, X. TRAIL and doxorubicin combination enhances anti-glioblastoma effect based on passive tumor targeting of liposomes. J. Control. Release 2011, 154, 93–102. [Google Scholar] [CrossRef] [PubMed]
- Bagci-Onder, T.; Agarwal, A.; Flusberg, D.; Wanningen, S.; Sorger, P.; Shah, K. Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors. Oncogene 2013, 32, 2818–2827. [Google Scholar] [CrossRef] [PubMed]
- Bago, J.R.; Alfonso-Pecchio, A.; Okolie, O.; Dumitru, R.; Rinkenbaugh, A.; Baldwin, A.S.; Miller, C.R.; Magness, S.T.; Hingtgen, S.D. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nat. Commun. 2016, 7, 10593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hingtgen, S.; Ren, X.; Terwilliger, E.; Classon, M.; Weissleder, R.; Shah, K. Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide. Mol. Cancer Ther. 2008, 7, 3575–3585. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, X.; Zhang, X.; Hu, S.; Zheng, M.; Zhang, J.; Zhao, J.; Zhang, X.; Yan, B.; Jia, L.; Zhao, J.; et al. Identification of miRNA-7 by genome-wide analysis as a critical sensitizer for TRAIL-induced apoptosis in glioblastoma cells. Nucleic Acids Res. 2017, 45, 5930–5944. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deng, X.; Zhao, W.; Song, L.; Ying, W.; Guo, X. Pro-apoptotic effect of TRAIL-transfected endothelial progenitor cells on glioma cells. Oncol. Lett. 2018, 15, 5004–5012. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bremer, E.; Samplonius, D.F.; van Genne, L.; Dijkstra, M.H.; Kroesen, B.J.; de Leij, L.F.; Helfrich, W. Simultaneous inhibition of epidermal growth factor receptor (EGFR) signaling and enhanced activation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated apoptosis induction by an scFv:sTRAIL fusion protein with specificity for human EGFR. J. Biol. Chem. 2005, 280, 10025–10033. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.H.; Ni, C.W.; Lin, Y.Z.; Yin, L.; Jiang, C.B.; Lv, C.T.; Le, Y.; Lang, Y.; Zhao, C.Y.; Yang, K.; et al. Targeted induction of apoptosis in glioblastoma multiforme cells by an MRP3-specific TRAIL fusion protein in vitro. Tumour Biol. 2014, 35, 1157–1168. [Google Scholar] [CrossRef] [PubMed]
- Vermot-Desroches, C.; Sergent, E.; Bonnin, B.; Wijdenes, J. Characterization of monoclonal antibodies directed against trail or trail receptors. Cell. Immunol. 2005, 236, 86–91. [Google Scholar] [CrossRef] [PubMed]
- George, J.; Banik, N.L.; Ray, S.K. Molecular Mechanisms of Taxol for Induction of Cell Death in Glioblastomas. Glioblastoma 2010, 283–298. [Google Scholar]
- George, J.; Banik, N.L.; Ray, S.K. Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth. J. Cell. Mol. Med. 2009, 13, 4205–4218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Unterkircher, T.; Cristofanon, S.; Vellanki, S.H.; Nonnenmacher, L.; Karpel-Massler, G.; Wirtz, C.R.; Debatin, K.M.; Fulda, S. Bortezomib primes glioblastoma, including glioblastoma stem cells, for TRAIL by increasing tBid stability and mitochondrial apoptosis. Clin. Cancer Res. 2011, 17, 4019–4030. [Google Scholar] [CrossRef] [PubMed]
- Fulda, S.; Meyer, E.; Debatin, K.M. Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression. Oncogene 2002, 21, 2283–2294. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Burton, T.R.; Henson, E.S.; Azad, M.B.; Brown, M.; Eisenstat, D.D.; Gibson, S.B. BNIP3 acts as transcriptional repressor of death receptor-5 expression and prevents TRAIL-induced cell death in gliomas. Cell Death Dis. 2013, 4, e587. [Google Scholar] [CrossRef] [PubMed]
- Allen, J.E.; Krigsfeld, G.; Mayes, P.A.; Patel, L.; Dicker, D.T.; Patel, A.S.; Dolloff, N.G.; Messaris, E.; Scata, K.A.; Wang, W.; et al. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci. Transl. Med. 2013, 5, 171ra117. [Google Scholar] [CrossRef] [PubMed]
- Tu, Y.S.; He, J.; Liu, H.; Lee, H.C.; Wang, H.; Ishizawa, J.; Allen, J.E.; Andreeff, M.; Orlowski, R.Z.; Davis, R.E.; et al. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma. Neoplasia 2017, 19, 772–780. [Google Scholar] [CrossRef] [PubMed]
- Kline, C.L.; Van den Heuvel, A.P.; Allen, J.E.; Prabhu, V.V.; Dicker, D.T.; El-Deiry, W.S. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2alpha kinases. Sci. Signal. 2016, 9, ra18. [Google Scholar] [CrossRef] [PubMed]
- Ni, X.; Zhang, X.; Hu, C.H.; Langridge, T.; Tarapore, R.S.; Allen, J.E.; Oster, W.; Duvic, M. ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways. Oncotarget 2017, 8, 61761–61776. [Google Scholar] [CrossRef] [PubMed]
- Darnell, J.E., Jr.; Kerr, I.M.; Stark, G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264, 1415–1421. [Google Scholar] [CrossRef] [PubMed]
- Allen, J.E.; Kline, C.L.; Prabhu, V.V.; Wagner, J.; Ishizawa, J.; Madhukar, N.; Lev, A.; Baumeister, M.; Zhou, L.; Lulla, A.; et al. Discovery and clinical introduction of first-in-class imipridone ONC201. Oncotarget 2016, 7, 74380–74392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karpel-Massler, G.; Ba, M.; Shu, C.; Halatsch, M.E.; Westhoff, M.A.; Bruce, J.N.; Canoll, P.; Siegelin, M.D. TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Oncotarget 2015, 6, 36456–36471. [Google Scholar] [CrossRef] [PubMed]
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Trejo-Solís, C.; Serrano-Garcia, N.; Escamilla-Ramírez, Á.; Castillo-Rodríguez, R.A.; Jimenez-Farfan, D.; Palencia, G.; Calvillo, M.; Alvarez-Lemus, M.A.; Flores-Nájera, A.; Cruz-Salgado, A.; et al. Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma. Int. J. Mol. Sci. 2018, 19, 3773. https://doi.org/10.3390/ijms19123773
Trejo-Solís C, Serrano-Garcia N, Escamilla-Ramírez Á, Castillo-Rodríguez RA, Jimenez-Farfan D, Palencia G, Calvillo M, Alvarez-Lemus MA, Flores-Nájera A, Cruz-Salgado A, et al. Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma. International Journal of Molecular Sciences. 2018; 19(12):3773. https://doi.org/10.3390/ijms19123773
Chicago/Turabian StyleTrejo-Solís, Cristina, Norma Serrano-Garcia, Ángel Escamilla-Ramírez, Rosa A. Castillo-Rodríguez, Dolores Jimenez-Farfan, Guadalupe Palencia, Minerva Calvillo, Mayra A. Alvarez-Lemus, Athenea Flores-Nájera, Arturo Cruz-Salgado, and et al. 2018. "Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma" International Journal of Molecular Sciences 19, no. 12: 3773. https://doi.org/10.3390/ijms19123773