Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status
Abstract
:1. Introduction
2. Results
2.1. Chondrosarcoma Cell Lines Are Variably Sensitive to PARP Inhibition, Irrespective of the IDH Mutation Status
2.2. PARP Inhibition Minimally Induces Apoptosis and Causes a G2/M Phase Cell Cycle Arrest in Chondrosarcoma Cell Lines
2.3. JJ012 Cells Have a Reduced Capacity to Sense DNA Damage, Independent of the IDH1 Mutation
2.4. Chondrosarcoma Cell Lines Are Homologous Recombination Proficient and Maintain Nominal Expression of ATM
2.5. The Combination of PARP Inhibition and Temozolomide Is Synergistic in Chondrosarcoma Cell Lines
2.6. PARP Inhibition Sensitizes Chondrosarcoma Cells to Radiation Which is Partially Rescued when Mutant IDH1 is Inhibited
3. Discussion
4. Materials and Methods
4.1. Compounds
4.2. Cell Culture
4.3. Cell Viability and Nuclei Count Assays
4.4. Apoptosis Assay
4.5. Cell Cycle Assay
4.6. Western Blotting
4.7. RAD51 Foci Assay
4.8. Next Generation RNA Sequencing Analysis
4.9. Methylation Array Analysis
4.10. Colony Formation Assay
4.11. Statistical Calculations and Image Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
References
- Hogendoorn, P.C.W.; Bovée, J.V.M.G.; Nielsen, G.P. Chondrosarcoma (grades I-III), including primary and secondary variants and periosteal chondrosarcoma. In WHO Classification of Tumours Soft Tissue and Bone; Fletcher, C.D.M., Bridge, J.A., Hogendoorn, P.C.W., Mertens, F., Eds.; IARC Press: Lyon, France, 2013; pp. 264–268. [Google Scholar]
- van Praag (Veroniek), V.M.; Rueten-Budde, A.J.; Ho, V.; Dijkstra, P.D.S.; van der Geest, I.C.; Bramer, J.A.; Schaap, G.R.; Jutte, P.C.; Schreuder, H.B.; Ploegmakers, J.J.W.; et al. Incidence, outcomes and prognostic factors during 25 years of treatment of chondrosarcomas. Surg. Oncol. 2018, 27, 402–408. [Google Scholar] [CrossRef] [PubMed]
- Gelderblom, H.; Hogendoorn, P.C.W.; Dijkstra, S.D.; van Rijswijk, C.S.; Krol, A.D.; Taminiau, A.H.M.; Bovee, J.V.M.G. The Clinical Approach Towards Chondrosarcoma. Oncologist 2008, 13, 320–329. [Google Scholar] [CrossRef] [PubMed]
- Amary, M.F.; Bacsi, K.; Maggiani, F.; Damato, S.; Halai, D.; Berisha, F.; Pollock, R.; O’Donnell, P.; Grigoriadis, A.; Diss, T.; et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J. Pathol. 2011, 224, 334–343. [Google Scholar] [CrossRef] [PubMed]
- Pansuriya, T.C.; Van Eijk, R.; D’Adamo, P.; Van Ruler, M.A.J.H.; Kuijjer, M.L.; Oosting, J.; Cleton-Jansen, A.M.; Van Oosterwijk, J.G.; Verbeke, S.L.J.; Meijer, D.; et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat. Genet. 2011, 43, 1256–1261. [Google Scholar] [CrossRef]
- Dang, L.; White, D.W.; Gross, S.; Bennett, B.D.; Bittinger, M.A.; Driggers, E.M.; Fantin, V.R.; Jang, H.G.; Jin, S.; Keenan, M.C.; et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009, 462, 739–744. [Google Scholar] [CrossRef]
- Molenaar, R.J.; Radivoyevitch, T.; Maciejewski, J.P.; van Noorden, C.J.F.; Bleeker, F.E. The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. Biochim. Biophys. Acta—Rev. Cancer 2014, 1846, 326–341. [Google Scholar] [CrossRef]
- Xu, W.; Yang, H.; Liu, Y.; Yang, Y.; Wang, P.; Kim, S.H.; Ito, S.; Yang, C.; Wang, P.; Xiao, M.T.; et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011, 19, 17–30. [Google Scholar] [CrossRef]
- Reitman, Z.J.; Jin, G.; Karoly, E.D.; Spasojevic, I.; Yang, J.; Kinzler, K.W.; He, Y.; Bigner, D.D.; Vogelstein, B.; Yan, H. Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc. Natl. Acad. Sci. USA 2011, 108, 3270–3275. [Google Scholar] [CrossRef]
- Gagné, L.M.; Boulay, K.; Topisirovic, I.; Huot, M.É.; Mallette, F.A. Oncogenic Activities of IDH1/2 Mutations: From Epigenetics to Cellular Signaling. Trends Cell Biol. 2017, 27, 738–752. [Google Scholar]
- Suijker, J.; Oosting, J.; Koornneef, A.; Struys, E.A.; Salomons, G.S.; Schaap, F.G.; Waaijer, C.J.F.; Wijers-Koster, P.M.; Briaire-de Bruijn, I.H.; Haazen, L.; et al. Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines. Oncotarget 2015, 6, 12505–12519. [Google Scholar] [CrossRef]
- Mardis, E.R.; Ding, L.; Dooling, D.J.; Larson, D.E.; McLellan, M.D.; Chen, K.; Koboldt, D.C.; Fulton, R.S.; Delehaunty, K.D.; McGrath, S.D.; et al. Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome. N. Engl. J. Med. 2009, 361, 1058–1066. [Google Scholar] [CrossRef] [PubMed]
- Yan, H.; Parsons, D.W.; Jin, G.; McLendon, R.; Rasheed, B.A.; Yuan, W.; Kos, I.; Batinic-Haberle, I.; Jones, S.; Riggins, G.J.; et al. IDH1 and IDH2 Mutations in Gliomas. N. Engl. J. Med. 2009, 360, 765–773. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.; Wu, J.; Ma, S.; Zhang, L.; Yao, J.; Hoadley, K.A.; Wilkerson, M.D.; Perou, C.M.; Guan, K.L.; Ye, D.; et al. Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. Cell Rep. 2015, 13, 2353–2361. [Google Scholar] [CrossRef] [PubMed]
- Inoue, S.; Li, W.Y.; Tseng, A.; Beerman, I.; Elia, A.J.; Bendall, S.C.; Lemonnier, F.; Kron, K.J.; Cescon, D.W.; Hao, Z.; et al. Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2. Cancer Cell 2016, 30, 337–348. [Google Scholar] [CrossRef] [PubMed]
- Chan, S.M.; Thomas, D.; Corces-Zimmerman, M.R.; Xavy, S.; Rastogi, S.; Hong, W.J.; Zhao, F.; Medeiros, B.C.; Tyvoll, D.A.; Majeti, R. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat. Med. 2015, 21, 178–184. [Google Scholar] [CrossRef] [PubMed]
- Karpel-Massler, G.; Ishida, C.T.; Bianchetti, E.; Zhang, Y.; Shu, C.; Tsujiuchi, T.; Banu, M.A.; Garcia, F.; Roth, K.A.; Bruce, J.N.; et al. Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL. Nat. Commun. 2017, 8, 1067. [Google Scholar] [CrossRef] [PubMed]
- Tateishi, K.; Wakimoto, H.; Iafrate, A.J.; Tanaka, S.; Loebel, F.; Lelic, N.; Wiederschain, D.; Bedel, O.; Deng, G.; Zhang, B.; et al. Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion. Cancer Cell 2015, 28, 773–784. [Google Scholar] [CrossRef]
- Emadi, A.; Jun, S.A.; Tsukamoto, T.; Fathi, A.T.; Minden, M.D.; Dang, C. V Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp. Hematol. 2014, 42, 247–251. [Google Scholar] [CrossRef]
- Sulkowski, P.L.; Corso, C.D.; Robinson, N.D.; Scanlon, S.E.; Purshouse, K.R.; Bai, H.; Liu, Y.; Sundaram, R.K.; Hegan, D.C.; Fons, N.R.; et al. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci. Transl. Med. 2017, 9, eaal2463. [Google Scholar] [CrossRef]
- Molenaar, R.J.; Radivoyevitch, T.; Nagata, Y.; Khurshed, M.; Przychodzen, B.; Makishima, H.; Xu, M.; Bleeker, F.E.; Wilmink, J.W.; Carraway, H.E.; et al. Idh1/2 mutations sensitize acute myeloid leukemia to parp inhibition and this is reversed by idh1/2-mutant inhibitors. Clin. Cancer Res. 2018, 24, 1705–1715. [Google Scholar] [CrossRef]
- Turcan, S.; Fabius, A.W.; Borodovsky, A.; Pedraza, A.; Brennan, C.; Huse, J.; Viale, A.; Riggins, G.J.; Chan, T.A. Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine. Oncotarget 2013, 4, 1729–1736. [Google Scholar] [CrossRef] [PubMed]
- Borodovsky, A.; Salmasi, V.; Turcan, S.; Fabius, A.W.M.; Baia, G.; Eberhart, C.G.; Weingart, J.D.; Gallia, G.L.; Baylin, S.B.; Chan, T.A.; et al. 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. Oncotarget 2013, 4, 1737–1747. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Aoyagi-Scharber, M.; Wang, B. Trapping Poly(ADP-Ribose) Polymerase. J. Pharmacol. Exp. Ther. 2015, 353, 446–457. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Rehman, F.L.; Feng, Y.; Boshuizen, J.; Bajrami, I.; Elliott, R.; Wang, B.; Lord, C.J.; Post, L.E.; Ashworth, A. BMN673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin. Cancer Res. 2013, 19, 5003–5015. [Google Scholar] [CrossRef]
- Engert, F.; Kovac, M.; Baumhoer, D.; Nathrath, M.; Fulda, S. Osteosarcoma cells with genetic signatures of BRCAness are susceptible to the PARP inhibitor talazoparib alone or in combination with chemotherapeutics. Oncotarget 2017, 8, 48794–48806. [Google Scholar] [CrossRef]
- Wilkerson, P.M.; Dedes, K.J.; Samartzis, E.P.; Dedes, I.; Lambros, M.B.; Natrajan, R.; Gauthier, A.; Piscuoglio, S.; Töpfer, C.; Vukovic, V.; et al. Preclinical evaluation of the PARP inhibitor BMN-673 for the treatment of ovarian clear cell cancer. Oncotarget 2017, 8, 6057–6066. [Google Scholar] [CrossRef]
- Naipal, K.A.T.; Verkaik, N.S.; Ameziane, N.; Van Deurzen, C.H.M.; Ter Brugge, P.; Meijers, M.; Sieuwerts, A.M.; Martens, J.W.; O’Connor, M.J.; Vrieling, H.; et al. Functional Ex vivo assay to select homologous recombination-deficient breast tumors for PARP inhibitor treatment. Clin. Cancer Res. 2014, 20, 4816–4826. [Google Scholar] [CrossRef]
- Typas, D.; Luijsterburg, M.S.; Wiegant, W.W.; Diakatou, M.; Helfricht, A.; Thijssen, P.E.; Van De Broek, B.; Mullenders, L.H.; Van Attikum, H. The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. Nucleic Acids Res. 2015, 43, 6919–6933. [Google Scholar] [CrossRef]
- Gill, S.J.; Travers, J.; Pshenichnaya, I.; Kogera, F.A.; Barthorpe, S.; Mironenko, T.; Richardson, L.; Benes, C.H.; Stratton, M.R.; McDermott, U.; et al. Combinations of PARP inhibitors with temozolomide drive PARP1 trapping and apoptosis in Ewing’s sarcoma. PLoS ONE 2015, 10, e0140988. [Google Scholar] [CrossRef]
- Smith, M.A.; Reynolds, C.P.; Kang, M.H.; Kolb, E.A.; Gorlick, R.; Carol, H.; Lock, R.B.; Keir, S.T.; Maris, J.M.; Billups, C.A.; et al. Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric Cancer Models in the Pediatric Preclinical Testing Program. Clin. Cancer Res. 2015, 21, 819–832. [Google Scholar] [CrossRef]
- Van Nifterik, K.A.; van den Berg, J.; van der Meide, W.F.; Ameziane, N.; Wedekind, L.E.; Steenbergen, R.D.M.; Leenstra, S.; Lafleur, M.V.M.; Slotman, B.J.; Stalpers, L.J.A.; et al. Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide. Br. J. Cancer 2010, 103, 29–35. [Google Scholar] [CrossRef] [PubMed]
- Ramakrishnan, V.; Kushwaha, D.; Koay, D.C.; Reddy, H.; Mao, Y.; Zhou, L.; Ng, K.; Zinn, P.; Carter, B.; Chen, C.C. Post-transcriptional regulation of O 6 -methylguanine-DNA methyltransferase MGMT in glioblastomas. Cancer Biomark. 2011, 10, 185–193. [Google Scholar] [CrossRef] [PubMed]
- Fertil, B.; Malaise, E.P. Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 1981, 7, 621–629. [Google Scholar] [CrossRef]
- Lu, Y.; Kwintkiewicz, J.; Liu, Y.; Tech, K.; Frady, L.N.; Su, Y.T.; Bautista, W.; Moon, S.I.; MacDonald, J.; Ewend, M.G.; et al. Chemosensitivity of IDH1-mutated gliomas due to an impairment in PARP1-mediated DNA repair. Cancer Res. 2017, 77, 1709–1718. [Google Scholar] [CrossRef] [Green Version]
- Tateishi, K.; Higuchi, F.; Miller, J.J.; Koerner, M.V.A.; Lelic, N.; Shankar, G.M.; Tanaka, S.; Fisher, D.E.; Batchelor, T.T.; Iafrate, A.J.; et al. The alkylating chemotherapeutic temozolomide induces metabolic stress in IDH1-mutant cancers and potentiates NAD+depletion-mediated cytotoxicity. Cancer Res. 2017, 77, 4102–4115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Jong, Y.; Monderer, D.; Brandinelli, E.; Monchanin, M.; van den Akker, B.E.; van Oosterwijk, J.G.; Blay, J.Y.; Dutour, A.; Bovée, J.V.M.G. Bcl-xl as the most promising Bcl-2 family member in targeted treatment of chondrosarcoma. Oncogenesis 2018, 7, 74. [Google Scholar] [CrossRef]
- Peterse, E.F.P.; van den Akker, B.E.W.M.; Niessen, B.; Oosting, J.; Suijker, J.; de Jong, Y.; Danen, E.H.J.; Cleton-Jansen, A.-M.; Bovée, J.V.M.G. NAD Synthesis Pathway Interference Is a Viable Therapeutic Strategy for Chondrosarcoma. Mol. Cancer Res. 2017, 15, 1714–1721. [Google Scholar] [CrossRef] [Green Version]
- Peterse, E.F.P.; Niessen, B.; Addie, R.D.; De Jong, Y.; Cleven, A.H.G.; Kruisselbrink, A.B.; Van Den Akker, B.E.W.M.; Molenaar, R.J.; Cleton-Jansen, A.M.; Bovée, J.V.M.G. Targeting glutaminolysis in chondrosarcoma in context of the IDH1/2 mutation. Br. J. Cancer 2018, 118, 1074–1083. [Google Scholar] [CrossRef] [Green Version]
- Núñez, F.J.; Mendez, F.M.; Kadiyala, P.; Alghamri, M.S.; Savelieff, M.G.; Garcia-Fabiani, M.B.; Haase, S.; Koschmann, C.; Calinescu, A.-A.; Kamran, N.; et al. IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response. Sci. Transl. Med. 2019, 11, eaaq1427. [Google Scholar] [CrossRef]
- Hafner, M.; Niepel, M.; Chung, M.; Sorger, P.K. Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs. Nat. Methods 2016, 13, 521–527. [Google Scholar] [CrossRef]
- Smeenk, G.; Wiegant, W.W.; Marteijn, J.A.; Luijsterburg, M.S.; Sroczynski, N.; Costelloe, T.; Romeijn, R.J.; Pastink, A.; Mailand, N.; Vermeulen, W.; et al. Poly(ADP-ribosyl)ation links the chromatin remodeler SMARCA5/SNF2H to RNF168-dependent DNA damage signaling. J. Cell Sci. 2012, 126, 889–903. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ciccarone, F.; Zampieri, M.; Caiafa, P. PARP1 orchestrates epigenetic events setting up chromatin domains. Semin. Cell Dev. Biol. 2017, 63, 123–134. [Google Scholar] [CrossRef] [PubMed]
- Newton, M.D.; Makovets, S.; Krejci, L.; Kotenko, O.; Altmannova, V.; Vasianovich, Y. Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci. EMBO J. 2016, 36, 213–231. [Google Scholar]
- de Jong, Y.; Ingola, M.; Briaire-de Bruijn, I.H.; Kruisselbrink, A.B.; Venneker, S.; Palubeckaite, I.; Heijs, B.P.A.M.; Cleton-Jansen, A.-M.; Haas, R.L.M.; Bovée, J.V.M.G. Radiotherapy resistance in chondrosarcoma cells; a possible correlation with alterations in cell cycle related genes. Clin. Sarcoma Res. 2019, 9, 9. [Google Scholar] [CrossRef]
- Wei, H.; Yu, X. Functions of PARylation in DNA Damage Repair Pathways. Genom. Proteom. Bioinfo. 2016, 14, 131–139. [Google Scholar] [CrossRef] [Green Version]
- Césaire, M.; Ghosh, U.; Austry, J.-B.; Muller, E.; Cammarata, F.P.; Guillamin, M.; Caruso, M.; Castéra, L.; Petringa, G.; Cirrone, G.A.P.; et al. Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation. J. Bone Oncol. 2019, 17, 100246. [Google Scholar] [CrossRef]
- Murai, J.; Zhang, Y.; Morris, J.; Ji, J.; Takeda, S.; Doroshow, J.H.; Pommier, Y. Rationale for Poly(ADP-ribose) Polymerase (PARP) Inhibitors in Combination Therapy with Camptothecins or Temozolomide Based on PARP Trapping versus Catalytic Inhibition. J. Pharmacol. Exp. Ther. 2014, 349, 408–416. [Google Scholar] [CrossRef] [Green Version]
- de Bono, J.; Ramanathan, R.K.; Mina, L.; Chugh, R.; Glaspy, J.; Rafii, S.; Kaye, S.; Sachdev, J.; Heymach, J.; Smith, D.C.; et al. Phase I, dose-escalation, two-part trial of the PARP inhibitor talazoparib in patients with advanced germline BRCA1/2 mutations and selected sporadic cancers. Cancer Discov. 2017, 7, 620–629. [Google Scholar] [CrossRef] [Green Version]
- Brada, M.; Judson, I.; Beale, P.; Moore, S.; Reidenberg, P.; Statkevich, P.; Dugan, M.; Batra, V.; Cutler, D. Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br. J. Cancer 1999, 81, 1022–1030. [Google Scholar] [CrossRef]
- Gil-Benso, R.; Lopez-Gines, C.; López-Guerrero, J.A.; Carda, C.; Callaghan, R.C.; Navarro, S.; Ferrer, J.; Pellín, A.; Llombart-Bosch, A. Establishment and characterization of a continuous human chondrosarcoma cell line, ch-2879: Comparative histologic and genetic studies with its tumor of origin. Lab. Investig. 2003, 83, 877–887. [Google Scholar] [CrossRef] [Green Version]
- Scully, S.P.; Berend, K.R.; Toth, A.; Qi, W.N.; Qi, Z.; Block, J.A. Interstitial collagenase gene expression correlates with in vitro invasion in human chondrosarcoma. Clin. Orthop. Relat. Res. 2000, 376, 291–303. [Google Scholar] [CrossRef] [PubMed]
- Calabuig-Fariñas, S.; Benso, R.G.; Szuhai, K.; Machado, I.; López-Guerrero, J.A.; De Jong, D.; Peydró, A.; Miguel, T.S.; Navarro, L.; Pellín, A.; et al. Characterization of a new human cell line (CH-3573) derived from a grade II chondrosarcoma with matrix production. Pathol. Oncol. Res. 2012, 18, 793–802. [Google Scholar] [CrossRef] [PubMed]
- van Oosterwijk, J.G.; de Jong, D.; van Ruler, M.A.; Hogendoorn, P.C.; Dijkstra, P.D.S.; van Rijswijk, C.S.; Machado, I.; Llombart-Bosch, A.; Szuhai, K.; Bovée, J.V. Three new chondrosarcoma cell lines: One grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone. BMC Cancer 2012, 12, 375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kudo, N.; Ogose, A.; Hotta, T.; Kawashima, H.; Gu, W.; Umezu, H.; Toyama, T.; Endo, N. Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation. Virchows Arch. 2007, 451, 691–699. [Google Scholar] [CrossRef] [PubMed]
- Rasheed, S.; Nelson-Rees, W.A.; Toth, E.M.; Arnstein, P.; Gardner, M.B. Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer 1974, 33, 1027–1033. [Google Scholar] [CrossRef]
- De Jong, Y.; Van Maldegem, A.M.; Marino-Enriquez, A.; De Jong, D.; Suijker, J.; Briaire-De Bruijn, I.H.; Kruisselbrink, A.B.; Cleton-Jansen, A.M.; Szuhai, K.; Gelderblom, H.; et al. Inhibition of Bcl-2 family members sensitizes mesenchymal chondrosarcoma to conventional chemotherapy: Report on a novel mesenchymal chondrosarcoma cell line. Lab. Investig. 2016, 96, 1128–1137. [Google Scholar] [CrossRef]
- Van Haaften, C.; Boot, A.; Corver, W.E.; Van Eendenburg, J.D.; Trimbos, B.J.; Van Wezel, T. Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells. J. Exp. Clin. Cancer Res. 2015, 34, 38. [Google Scholar] [CrossRef] [Green Version]
- Corver, W.E.; Demmers, J.; Oosting, J.; Sahraeian, S.; Boot, A.; Ruano, D.; Van Wezel, T.; Morreau, H. ROS-induced near-homozygous genomes in thyroid cancer. Endocr. Relat. Cancer 2018, 25, 83–97. [Google Scholar] [CrossRef]
- Franken, N.A.P.; Rodermond, H.M.; Stap, J.; Haveman, J.; van Bree, C. Clonogenic assay of cells in vitro. Nat. Protoc. 2006, 1, 2315–2319. [Google Scholar] [CrossRef]
- Greco, W.; Bravo, G.; Parsons, J. The search for Synergy: A critical review from a repsonse persepective. Pharmacol. Rev. 1995, 47, 331–385. [Google Scholar]
- Borisy, A.A.; Elliott, P.J.; Hurst, N.W.; Lee, M.S.; Lehar, J.; Price, E.R.; Serbedzija, G.; Zimmermann, G.R.; Foley, M.A.; Stockwell, B.R.; et al. Systematic discovery of multicomponent therapeutics. Proc. Natl. Acad. Sci. USA 2003, 100, 7977–7982. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Cell Line | Chondrosarcoma Subtype | IDH Mutation Status | GR50 (nM) | IC50 (nM) | GRInf (%) | EInf (%) |
---|---|---|---|---|---|---|
NDCS1 | Dedifferentiated | Wildtype | 34 | 25 | −54 | 0 |
MCS170 | Mesenchymal | Wildtype | 75 | - | 7 | 57 |
SW1353 | Central conventional | IDH2 R172S | 133 | 63 | −25 | 3 |
HT1080 | Dedifferentiated | IDH1 R132C | 188 | 61 | 10 | 11 |
CH3573 | Central conventional | Wildtype | 244 | 471 | −2 | 26 |
L2975 | Dedifferentiated | IDH2 R172W | 326 | 401 | 1 | 22 |
JJ012 | Central conventional | IDH1 R132G | 371 | 193 | −23 | 1 |
JJ012 + AGI-5198 | Central conventional | “Wildtype” | 659 | 303 | −11 | 0 |
L3252B | Dedifferentiated | Wildtype | 876 | 1442 | −75 | 0 |
L835 | Central conventional | IDH1 R132C | 1670 | - | 12 | 68 |
CH2879 | Central conventional | Wildtype | 1726 | 1103 | −90 | 1 |
CH2879 + AGI-5198 | Central conventional | Wildtype | 4280 | 4060 | −16 | 22 |
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Venneker, S.; Kruisselbrink, A.B.; Briaire-de Bruijn, I.H.; de Jong, Y.; van Wijnen, A.J.; Danen, E.H.J.; Bovée, J.V.M.G. Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status. Cancers 2019, 11, 1918. https://doi.org/10.3390/cancers11121918
Venneker S, Kruisselbrink AB, Briaire-de Bruijn IH, de Jong Y, van Wijnen AJ, Danen EHJ, Bovée JVMG. Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status. Cancers. 2019; 11(12):1918. https://doi.org/10.3390/cancers11121918
Chicago/Turabian StyleVenneker, Sanne, Alwine B. Kruisselbrink, Inge H. Briaire-de Bruijn, Yvonne de Jong, Andre J. van Wijnen, Erik H.J. Danen, and Judith V.M.G. Bovée. 2019. "Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status" Cancers 11, no. 12: 1918. https://doi.org/10.3390/cancers11121918
APA StyleVenneker, S., Kruisselbrink, A. B., Briaire-de Bruijn, I. H., de Jong, Y., van Wijnen, A. J., Danen, E. H. J., & Bovée, J. V. M. G. (2019). Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status. Cancers, 11(12), 1918. https://doi.org/10.3390/cancers11121918