Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
Abstract
:1. Introduction
2. Pro-Oxidative Drugs in Preclinical Study
2.1. Phytochemicals with a Characterized Mechanism of of ROS Induction
2.1.1. Piperlongumine
2.1.2. Resveratrol
2.1.3. Oleanolic Acid
2.1.4. Plumbagin
2.1.5. Capsaicin
2.1.6. Celastrol
2.2. Pro-Oxidative Phytochemicals with Uncharacterized Mechanism of ROS Induction
2.3. Small Molecules
2.3.1. LCS-1
2.3.2. 15-Deoxy-Δ12,14-prostaglandin J2
2.3.3. Tetraethylthiuram Disulfide
3. Pro-Oxidative Drugs in the Clinical Setting
3.1. Pro-Oxidative Drugs in Clinical Trials
3.1.1. Choline Tetrathiomolybdate (ATN-224)
3.1.2. 2-Methoxyoestradiol
3.1.3. Curcumin and Its Derivatives
3.2. Pro-Oxidative Drugs in Clinical Use
3.2.1. Cisplatin
3.2.2. Doxorubicin
4. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
Abbreviations
15d-PGJ2 | 15-deoxy-Δ12,14-prostaglandin J2. |
ATN-224 | Choline tetrathiomolybdate. |
DSF | Tetraethylthiuram disulfide. |
ER | Endoplasmic reticulum. |
LCS-1 | Lung cancer screen 1. |
NO | Nitric oxide. |
OA | Oleanolic acid. |
PPAR-γ | Peroxisome proliferator-activated receptor gamma. |
PPL | Piperlongumine. |
ROS | Reactive oxygen species. |
SOD | Superoxide dismutase. |
TrxR | Thioredoxin reductase. |
References
- Liou, G.-Y.; Storz, P. Reactive oxygen species in cancer. Free Radic. Res. 2010, 44, 479–496. [Google Scholar] [CrossRef]
- Reczek, C.R.; Chandel, N.S. The Two Faces of Reactive Oxygen Species in Cancer. Annu. Rev. Cancer Biol. 2017, 1, 79–98. [Google Scholar] [CrossRef]
- Yang, H.; Villani, R.M.; Wang, H.; Simpson, M.J.; Roberts, M.S.; Tang, M.; Liang, X. The role of cellular reactive oxygen species in cancer chemotherapy. J. Exp. Clin. Cancer Res. 2018, 37, 266. [Google Scholar] [CrossRef]
- Sies, H.; Jones, D.P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 2020, 21, 363–383. [Google Scholar] [CrossRef]
- Wang, Y.; Qi, H.; Liu, Y.; Duan, C.; Liu, X.; Xia, T.; Chen, D.; Piao, H.; Liu, H.-X. The double-edged roles of ROS in cancer prevention and therapy. Theranostics 2021, 11, 4839–4857. [Google Scholar] [CrossRef] [PubMed]
- Weinberg, F.; Ramnath, N.; Nagrath, D. Reactive Oxygen Species in the Tumor Microenvironment: An Overview. Cancers 2019, 11, 1191. [Google Scholar] [CrossRef] [PubMed]
- Felty, Q.; Singh, K.P.; Roy, D. Estrogen-induced G1/S transition of G0-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling. Oncogene 2005, 24, 4883–4893. [Google Scholar] [CrossRef]
- Weinberg, F.; Hamanaka, R.; Wheaton, W.W.; Weinberg, S.; Joseph, J.; Lopez, M.; Kalyanaraman, B.; Mutlu, G.M.; Budinger, G.R.S.; Chandel, N.S. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl. Acad. Sci. USA 2010, 107, 8788–8793. [Google Scholar] [CrossRef]
- Ferrara, N. VEGF-A: A critical regulator of blood vessel growth. Eur. Cytokine Netw. 2009, 20, 158–163. [Google Scholar] [CrossRef]
- Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A. ROS in cancer therapy: The bright side of the moon. Exp. Mol. Med. 2020, 52, 192–203. [Google Scholar] [CrossRef] [PubMed]
- Che, M.; Wang, R.; Li, X.; Wang, H.-Y.; Zheng, X.F.S. Expanding roles of superoxide dismutases in cell regulation and cancer. Drug Discov. Today 2016, 21, 143–149. [Google Scholar] [CrossRef] [PubMed]
- Choudhari, A.S.; Mandave, P.C.; Deshpande, M.; Ranjekar, P.; Prakash, O. Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice. Front. Pharmacol. 2020, 10, 1614. [Google Scholar] [CrossRef] [PubMed]
- Parama, D.; Rana, V.; Girisa, S.; Verma, E.; Daimary, U.D.; Thakur, K.K.; Kumar, A.; Kunnumakkara, A.B. The promising potential of piperlongumine as an emerging therapeutics for cancer. Explor. Target. Anti-Tumor Ther. 2021, 2, 323–354. [Google Scholar] [CrossRef]
- Tripathi, S.K.; Biswal, B.K. Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacol. Res. 2020, 156, 104772. [Google Scholar] [CrossRef]
- Zhang, Q.; Chen, W.; Lv, X.; Weng, Q.; Chen, M.; Cui, R.; Liang, G.; Ji, J. Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress. Front. Pharmacol. 2019, 10, 1180. [Google Scholar] [CrossRef]
- Seok, J.S.; Jeong, C.H.; Petriello, M.C.; Seo, H.G.; Yoo, H.; Hong, K.; Han, S.G. Piperlongumine decreases cell proliferation and the expression of cell cycle-associated proteins by inhibiting Akt pathway in human lung cancer cells. Food Chem. Toxicol. 2018, 111, 9–18. [Google Scholar] [CrossRef]
- Wang, H.; Jiang, H.; Corbet, C.; de Mey, S.; Law, K.; Gevaert, T.; Feron, O.; De Ridder, M. Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems. Cancer Lett. 2019, 450, 42–52. [Google Scholar] [CrossRef]
- Roh, J.-L.; Kim, E.H.; Park, J.Y.; Kim, J.W.; Kwon, M.; Lee, B.-H. Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer. Oncotarget 2014, 5, 9227–9238. [Google Scholar] [CrossRef]
- Zhang, P.; Shi, L.; Zhang, T.; Hong, L.; He, W.; Cao, P.; Shen, X.; Zheng, P.; Xia, Y.; Zou, P. Piperlongumine potentiates the antitumor efficacy of oxaliplatin through ROS induction in gastric cancer cells. Cell. Oncol. 2019, 42, 847–860. [Google Scholar] [CrossRef] [PubMed]
- Zheng, L.; Fang, S.; Chen, A.; Chen, W.; Qiao, E.; Chen, M.; Shu, G.; Zhang, D.; Kong, C.; Weng, Q.; et al. Piperlongumine synergistically enhances the antitumour activity of sorafenib by mediating ROS-AMPK activation and targeting CPSF7 in liver cancer. Pharmacol. Res. 2022, 177, 106140. [Google Scholar] [CrossRef]
- Li, P.; Guo, X.; Liu, T.; Liu, Q.; Yang, J.; Liu, G. Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1–3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice. Mol. Pharm. 2022, 19, 4576–4587. [Google Scholar] [CrossRef] [PubMed]
- Choi, D.G.; Venkatesan, J.; Shim, M.S. Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan–Fucoidan Nanoparticles. Int. J. Mol. Sci. 2019, 20, 3220. [Google Scholar] [CrossRef] [PubMed]
- Salehi, B.; Mishra, A.; Nigam, M.; Sener, B.; Kilic, M.; Sharifi-Rad, M.; Fokou, P.; Martins, N.; Sharifi-Rad, J. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines 2018, 6, 91. [Google Scholar] [CrossRef]
- Martins, L.A.M.; Coelho, B.P.; Behr, G.; Pettenuzzo, L.F.; Souza, I.C.C.; Moreira, J.C.F.; Borojevic, R.; Gottfried, C.; Guma, F.C.R. Resveratrol Induces Pro-oxidant Effects and Time-Dependent Resistance to Cytotoxicity in Activated Hepatic Stellate Cells. Cell Biochem. Biophys. 2014, 68, 247–257. [Google Scholar] [CrossRef]
- San Hipólito-Luengo, Á.; Alcaide, A.; Ramos-González, M.; Cercas, E.; Vallejo, S.; Romero, A.; Talero, E.; Sánchez-Ferrer, C.F.; Motilva, V.; Peiró, C. Dual Effects of Resveratrol on Cell Death and Proliferation of Colon Cancer Cells. Nutr. Cancer 2017, 69, 1019–1027. [Google Scholar] [CrossRef]
- Miki, H.; Uehara, N.; Kimura, A.; Sasaki, T.; Yuri, T.; Yoshizawa, K.; Tsubura, A. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int. J. Oncol. 2012, 40, 1020–1028. [Google Scholar] [CrossRef]
- Cheng, L.; Yan, B.; Chen, K.; Jiang, Z.; Zhou, C.; Cao, J.; Qian, W.; Li, J.; Sun, L.; Ma, J.; et al. Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways. Oxid. Med. Cell. Longev. 2018, 2018, 9482018. [Google Scholar] [CrossRef] [PubMed]
- Almeida, T.C.; Melo, A.S.; Lima, A.P.B.; Branquinho, R.T.; da Silva, G.N. Resveratrol induces the production of reactive oxygen species, interferes with the cell cycle, and inhibits the cell migration of bladder tumour cells with different TP53 status. Nat. Prod. Res. 2022, 1–6. [Google Scholar] [CrossRef]
- Ma, F.; Ma, Y.; Liu, K.; Gao, J.; Li, S.; Sun, X.; Li, G. Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1–DYRK1A–EGFR axis. Food Funct. 2023, 14, 1484–1497. [Google Scholar] [CrossRef]
- Zhang, L.; Dai, F.; Sheng, P.; Chen, Z.; Xu, Q.; Guo, Y. Resveratrol analogue 3,4,4′-trihydroxy-trans-stilbene induces apoptosis and autophagy in human non-small-cell lung cancer cells in vitro. Acta Pharmacol. Sin. 2015, 36, 1256–1265. [Google Scholar] [CrossRef]
- Çınar Ayan, İ.; Güçlü, E.; Vural, H.; Dursun, H.G. Piceatannol induces apoptotic cell death through activation of caspase-dependent pathway and upregulation of ROS-mediated mitochondrial dysfunction in pancreatic cancer cells. Mol. Biol. Rep. 2022, 49, 11947–11957. [Google Scholar] [CrossRef]
- Li, C.; Wang, Z.; Lei, H.; Zhang, D. Recent progress in nanotechnology-based drug carriers for resveratrol delivery. Drug Deliv. 2023, 30, 2174206. [Google Scholar] [CrossRef] [PubMed]
- Shanmugam, M.K.; Dai, X.; Kumar, A.P.; Tan, B.K.H.; Sethi, G.; Bishayee, A. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence. Cancer Lett. 2014, 346, 206–216. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Song, Y.; Zhang, P.; Zhu, H.; Chen, L.; Xiao, Y.; Xing, Y. Oleanolic acid inhibits cell survival and proliferation of prostate cancer cells in vitro and in vivo through the PI3K/Akt pathway. Tumor Biol. 2016, 37, 7599–7613. [Google Scholar] [CrossRef]
- Liu, J.; Wu, N.; Ma, L.-N.; Zhong, J.-T.; Liu, G.; Zheng, L.-H.; Lin, X.-K. p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid. Asian Pac. J. Cancer Prev. 2014, 15, 4519–4525. [Google Scholar] [CrossRef]
- Gao, L.; Wang, Y.; Xu, Z.; Li, X.; Wu, J.; Liu, S.; Chu, P.; Sun, Z.; Sun, B.; Lin, Y.; et al. SZC017, a novel oleanolic acid derivative, induces apoptosis and autophagy in human breast cancer cells. Apoptosis 2015, 20, 1636–1650. [Google Scholar] [CrossRef]
- Cheng, B.; Chu, X.; Liu, R.; Ma, X.; Wang, M.; Zhang, J.; Jiao, P.; Gao, Q.; Ma, W.; Zhang, Y.; et al. Synthesis of Novel Pentacyclic Triterpenoid Derivatives that Induce Apoptosis in Cancer Cells through a ROS-dependent, Mitochondrial-Mediated Pathway. Mol. Pharm. 2023, 20, 701–710. [Google Scholar] [CrossRef] [PubMed]
- Akuetteh, P.D.P.; Huang, H.; Wu, S.; Zhou, H.; Jin, G.; Hong, W.; Yang, H.; Lan, L.; Shangguan, F.; Zhang, Q. Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. J. Biochem. Mol. Toxicol. 2022, 36, e23192. [Google Scholar] [CrossRef]
- Narożna, M.; Krajka-Kuźniak, V.; Bednarczyk-Cwynar, B.; Kucińska, M.; Kleszcz, R.; Kujawski, J.; Piotrowska-Kempisty, H.; Plewiński, A.; Murias, M.; Baer-Dubowska, W. Conjugation of Diclofenac with Novel Oleanolic Acid Derivatives Modulate Nrf2 and NF-κB Activity in Hepatic Cancer Cells and Normal Hepatocytes Leading to Enhancement of Its Therapeutic and Chemopreventive Potential. Pharmaceuticals 2021, 14, 688. [Google Scholar] [CrossRef]
- Bian, M.; Sun, Y.; Liu, Y.; Xu, Z.; Fan, R.; Liu, Z.; Liu, W. A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti-Ovarian-Cancer Agent by Inhibiting TrxR and Activating ROS-Mediated ERS. Chem. Eur. J. 2020, 26, 7092–7108. [Google Scholar] [CrossRef]
- Narożna, M.; Krajka-Kuźniak, V.; Kleszcz, R.; Bednarczyk-Cwynar, B.; Szaefer, H.; Baer-Dubowska, W. Activation of the Nrf2 response by oleanolic acid oxime morpholide (3-hydroxyiminoolean-12-en-28-oic acid morpholide) is associated with its ability to induce apoptosis and inhibit proliferation in HepG2 hepatoma cells. Eur. J. Pharmacol. 2020, 883, 173307. [Google Scholar] [CrossRef]
- Liese, J.; Hinrichs, T.M.; Lange, M.; Fulda, S. Cotreatment with sorafenib and oleanolic acid induces reactive oxygen species-dependent and mitochondrial-mediated apoptotic cell death in hepatocellular carcinoma cells. Anticancer Drugs 2019, 30, 209–217. [Google Scholar] [CrossRef]
- Zhu, B.; Ren, C.; Du, K.; Zhu, H.; Ai, Y.; Kang, F.; Luo, Y.; Liu, W.; Wang, L.; Xu, Y.; et al. Olean-28,13b-olide 2 plays a role in cisplatin-mediated apoptosis and reverses cisplatin resistance in human lung cancer through multiple signaling pathways. Biochem. Pharmacol. 2019, 170, 113642. [Google Scholar] [CrossRef]
- Lange, M.; Abhari, B.A.; Hinrichs, T.M.; Fulda, S.; Liese, J. Identification of a novel oxidative stress induced cell death by Sorafenib and oleanolic acid in human hepatocellular carcinoma cells. Biochem. Pharmacol. 2016, 118, 9–17. [Google Scholar] [CrossRef]
- Yin, Z.; Zhang, J.; Chen, L.; Guo, Q.; Yang, B.; Zhang, W.; Kang, W. Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances. BioMed Res. Int. 2020, 2020, 6940953. [Google Scholar] [CrossRef]
- Hwang, G.H.; Ryu, J.M.; Jeon, Y.J.; Choi, J.; Han, H.J.; Lee, Y.-M.; Lee, S.; Bae, J.-S.; Jung, J.-W.; Chang, W.; et al. The role of thioredoxin reductase and glutathione reductase in plumbagin-induced, reactive oxygen species-mediated apoptosis in cancer cell lines. Eur. J. Pharmacol. 2015, 765, 384–393. [Google Scholar] [CrossRef]
- Zhang, J.; Peng, S.; Li, X.; Liu, R.; Han, X.; Fang, J. Targeting thioredoxin reductase by plumbagin contributes to inducing apoptosis of HL-60 cells. Arch. Biochem. Biophys. 2017, 619, 16–26. [Google Scholar] [CrossRef]
- Tripathi, S.K.; Rengasamy, K.R.R.; Biswal, B.K. Plumbagin engenders apoptosis in lung cancer cells via caspase-9 activation and targeting mitochondrial-mediated ROS induction. Arch. Pharm. Res. 2020, 43, 242–256. [Google Scholar] [CrossRef]
- Jaiswal, A.; Sabarwal, A.; Narayan Mishra, J.P.; Singh, R.P. Plumbagin induces ROS-mediated apoptosis and cell cycle arrest and inhibits EMT in human cervical carcinoma cells. RSC Adv. 2018, 8, 32022–32037. [Google Scholar] [CrossRef]
- Srinivas, P.; Gopinath, G.; Banerji, A.; Dinakar, A.; Srinivas, G. Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol. Carcinog. 2004, 40, 201–211. [Google Scholar] [CrossRef]
- Pandey, K.; Tripathi, S.K.; Panda, M.; Biswal, B.K. Prooxidative activity of plumbagin induces apoptosis in human pancreatic ductal adenocarcinoma cells via intrinsic apoptotic pathway. Toxicol. Vitro 2020, 65, 104788. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.-L.; Yu, C.-I.; Lee, T.-H.; Chuang, J.M.-J.; Han, K.-F.; Lin, C.-S.; Huang, W.-P.; Chen, J.Y.-F.; Chen, C.-Y.; Lin, M.-Y.; et al. Plumbagin induces the apoptosis of drug-resistant oral cancer in vitro and in vivo through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction. Phytomedicine 2023, 111, 154655. [Google Scholar] [CrossRef] [PubMed]
- Xue, D.; Pan, S.-T.; Zhou, X.; Ye, F.; Zhou, Q.; Shi, F.; He, F.; Yu, H.; Qiu, J. Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma. Oxid. Med. Cell. Longev. 2020, 2020, 5649174. [Google Scholar] [CrossRef] [PubMed]
- Chao, C.-C.; Hou, S.-M.; Huang, C.C.; Hou, C.-H.; Chen, P.-C.; Liu, J.-F. Plumbagin induces apoptosis in human osteosarcoma through ROS generation, endoplasmic reticulum stress and mitochondrial apoptosis pathway. Mol. Med. Rep. 2017, 16, 5480–5488. [Google Scholar] [CrossRef] [PubMed]
- Huang, H.; Xie, H.; Pan, Y.; Zheng, K.; Xia, Y.; Chen, W. Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS. Cell. Physiol. Biochem. 2018, 45, 267–280. [Google Scholar] [CrossRef]
- Zhou, S.-F.; Pan, S.-T.; Qin, Y.; Zhou, Z.-W.; He, Z.; Zhang, X.; Yang, T.; Yang, Y.-X.; Wang, D.; Qiu, J. Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells. Drug Des. Devel. Ther. 2015, 9, 1601. [Google Scholar] [CrossRef]
- Xu, T.-P.; Shen, H.; Liu, L.-X.; Shu, Y.-Q. Plumbagin from Plumbago Zeylanica L Induces Apoptosis in Human Non-small Cell Lung Cancer Cell Lines through NF-κB Inactivation. Asian Pac. J. Cancer Prev. 2013, 14, 2325–2331. [Google Scholar] [CrossRef]
- Zhang, R.; Wang, Z.; You, W.; Zhou, F.; Guo, Z.; Qian, K.; Xiao, Y.; Wang, X. Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT. Cancer Cell Int. 2020, 20, 520. [Google Scholar] [CrossRef]
- Checker, R.; Gambhir, L.; Sharma, D.; Kumar, M.; Sandur, S.K. Plumbagin induces apoptosis in lymphoma cells via oxidative stress mediated glutathionylation and inhibition of mitogen-activated protein kinase phosphatases (MKP1/2). Cancer Lett. 2015, 357, 265–278. [Google Scholar] [CrossRef]
- Abedinpour, P.; Baron, V.T.; Chrastina, A.; Rondeau, G.; Pelayo, J.; Welsh, J.; Borgström, P. Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study. Prostate 2017, 77, 1550–1562. [Google Scholar] [CrossRef]
- Adetunji, T.L.; Olawale, F.; Olisah, C.; Adetunji, A.E.; Aremu, A.O. Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer. Front. Oncol. 2022, 12, 908487. [Google Scholar] [CrossRef]
- Zhang, S.; Wang, D.; Huang, J.; Hu, Y.; Xu, Y. Application of capsaicin as a potential new therapeutic drug in human cancers. J. Clin. Pharm. Ther. 2020, 45, 16–28. [Google Scholar] [CrossRef]
- Yang, K.; Pyo, J.; Kim, G.-Y.; Yu, R.; Han, I.; Ju, S.; Kim, W.; Kim, B.-S. Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Cell. Mol. Biol. Lett. 2009, 14, 3. [Google Scholar] [CrossRef]
- Sánchez, A.M.; Sánchez, M.G.; Malagarie-Cazenave, S.; Olea, N.; Díaz-Laviada, I. Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 2006, 11, 89–99. [Google Scholar] [CrossRef]
- Sánchez, A.M.; Malagarie-Cazenave, S.; Olea, N.; Vara, D.; Chiloeches, A.; Díaz-Laviada, I. Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 2007, 12, 2013–2024. [Google Scholar] [CrossRef]
- Yang, Z.-H.; Wang, X.-H.; Wang, H.-P.; Hu, L.-Q.; Zheng, X.-M.; Li, S.-W. Capsaicin Mediates Cell Death in Bladder Cancer T24 Cells Through Reactive Oxygen Species Production and Mitochondrial Depolarization. Urology 2010, 75, 735–741. [Google Scholar] [CrossRef]
- Lee, J.-S.; Chang, J.-S.; Lee, J.Y.; Kim, J.-A. Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 Murine Bladder Tumor cells. Arch. Pharm. Res. 2004, 27, 1147–1153. [Google Scholar] [CrossRef]
- Qian, K.; Wang, G.; Cao, R.; Liu, T.; Qian, G.; Guan, X.; Guo, Z.; Xiao, Y.; Wang, X. Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways. Molecules 2016, 21, 1406. [Google Scholar] [CrossRef]
- Hacioglu, C. Capsaicin inhibits cell proliferation by enhancing oxidative stress and apoptosis through SIRT1/NOX4 signaling pathways in HepG2 and HL-7702 cells. J. Biochem. Mol. Toxicol. 2022, 36, e22974. [Google Scholar] [CrossRef]
- Pramanik, K.C.; Boreddy, S.R.; Srivastava, S.K. Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells. PLoS ONE 2011, 6, e20151. [Google Scholar] [CrossRef]
- Shi, J.; Li, J.; Xu, Z.; Chen, L.; Luo, R.; Zhang, C.; Gao, F.; Zhang, J.; Fu, C. Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application. Front. Pharmacol. 2020, 11, 558741. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Fan, Y.; Li, D.; Han, B.; Meng, Y.; Chen, F.; Liu, T.; Song, Z.; Han, Y.; Huang, L.; et al. Ferroptosis inducer erastin sensitizes NSCLC cells to celastrol through activation of the ROS–mitochondrial fission–mitophagy axis. Mol. Oncol. 2021, 15, 2084–2105. [Google Scholar] [CrossRef]
- Kim, J.H.; Lee, J.O.; Lee, S.K.; Kim, N.; You, G.Y.; Moon, J.W.; Sha, J.; Kim, S.J.; Park, S.H.; Kim, H.S. Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53–polo like kinase 2 (PLK-2) pathway. Cell. Signal. 2013, 25, 805–813. [Google Scholar] [CrossRef] [PubMed]
- Qi, B.; Qigao, Y.; Zhang, P.; Ren, Y.; Liu, H.; Liu, T.; Zhu, L.; Chen, Y. Celastrol enhances tamoxifen sensitivity in the treatment of triple negative breast cancer via mitochondria mediated apoptosis pathway. Am. J. Transl. Res. 2023, 15, 2703–2715. [Google Scholar]
- Moreira, H.; Szyjka, A.; Paliszkiewicz, K.; Barg, E. Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells. Oxid. Med. Cell. Longev. 2019, 2019, 6793957. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Zhao, H.; Ding, C.; Jiang, D.; Zhao, Z.; Li, Y.; Ding, X.; Gao, J.; Zhou, H.; Luo, C.; et al. Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1. Signal Transduct. Target. Ther. 2023, 8, 51. [Google Scholar] [CrossRef]
- Xu, L.-N.; Zhao, N.; Chen, J.-Y.; Ye, P.-P.; Nan, X.-W.; Zhou, H.-H.; Jiang, Q.-W.; Yang, Y.; Huang, J.-R.; Yuan, M.-L.; et al. Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo. Front. Oncol. 2019, 9, 2. [Google Scholar] [CrossRef]
- Chen, X.; Zhao, Y.; Luo, W.; Chen, S.; Lin, F.; Zhang, X.; Fan, S.; Shen, X.; Wang, Y.; Liang, G. Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells. Theranostics 2020, 10, 10290–10308. [Google Scholar] [CrossRef]
- Chadalapaka, G.; Jutooru, I.; Safe, S. Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells. Carcinogenesis 2012, 33, 886–894. [Google Scholar] [CrossRef]
- Chen, G.; Zhang, X.; Zhao, M.; Wang, Y.; Cheng, X.; Wang, D.; Xu, Y.; Du, Z.; Yu, X. Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells. BMC Cancer 2011, 11, 170. [Google Scholar] [CrossRef]
- Han, X.; Sun, S.; Zhao, M.; Cheng, X.; Chen, G.; Lin, S.; Guan, Y.; Yu, X. Celastrol Stimulates Hypoxia-Inducible Factor-1 Activity in Tumor Cells by Initiating the ROS/Akt/p70S6K Signaling Pathway and Enhancing Hypoxia-Inducible Factor-1α Protein Synthesis. PLoS ONE 2014, 9, e112470. [Google Scholar] [CrossRef]
- Nazim, U.; Yin, H.; Park, S. Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL-induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species. Mol. Med. Rep. 2018, 19, 984–993. [Google Scholar] [CrossRef]
- Wu, M.; Deng, C.; Lo, T.-H.; Chan, K.-Y.; Li, X.; Wong, C.-M. Peroxiredoxin, Senescence, and Cancer. Cells 2022, 11, 1772. [Google Scholar] [CrossRef]
- Thapa, P.; Jiang, H.; Ding, N.; Hao, Y.; Alshahrani, A.; Wei, Q. The Role of Peroxiredoxins in Cancer Development. Biology 2023, 12, 666. [Google Scholar] [CrossRef]
- Kim, Y.; Jang, H.H. The Role of Peroxiredoxin Family in Cancer Signaling. J. Cancer Prev. 2019, 24, 65–71. [Google Scholar] [CrossRef]
- Johnson, J.J. Carnosol: A promising anti-cancer and anti-inflammatory agent. Cancer Lett. 2011, 305, 1. [Google Scholar] [CrossRef]
- Park, K.-W.; Kundu, J.; Chae, I.-G.; Kim, D.-H.; Yu, M.-H.; Kundu, J.K.; Chun, K.-S. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int. J. Oncol. 2014, 44, 1309–1315. [Google Scholar] [CrossRef]
- Al Dhaheri, Y.; Attoub, S.; Ramadan, G.; Arafat, K.; Bajbouj, K.; Karuvantevida, N.; AbuQamar, S.; Eid, A.; Iratni, R. Carnosol Induces ROS-Mediated Beclin1-Independent Autophagy and Apoptosis in Triple Negative Breast Cancer. PLoS ONE 2014, 9, e109630. [Google Scholar] [CrossRef]
- Lo, Y.-C.; Lin, Y.-C.; Huang, Y.-F.; Hsieh, C.-P.; Wu, C.-C.; Chang, I.-L.; Chen, C.-L.; Cheng, C.-H.; Chen, H.-Y. Carnosol-Induced ROS Inhibits Cell Viability of Human Osteosarcoma by Apoptosis and Autophagy. Am. J. Chin. Med. 2017, 45, 1761–1772. [Google Scholar] [CrossRef]
- Alsamri, H.; El Hasasna, H.; Al Dhaheri, Y.; Eid, A.H.; Attoub, S.; Iratni, R. Carnosol, a Natural Polyphenol, Inhibits Migration, Metastasis, and Tumor Growth of Breast Cancer via a ROS-Dependent Proteasome Degradation of STAT3. Front. Oncol. 2019, 9, 743. [Google Scholar] [CrossRef]
- Alsamri, H.; Hasasna, H.E.; Baby, B.; Alneyadi, A.; Dhaheri, Y.A.; Ayoub, M.A.; Eid, A.H.; Vijayan, R.; Iratni, R. Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer. Front. Oncol. 2021, 11, 664403. [Google Scholar] [CrossRef] [PubMed]
- Alsamri, H.; Alneyadi, A.; Muhammad, K.; Ayoub, M.A.; Eid, A.; Iratni, R. Carnosol Induces p38-Mediated ER Stress Response and Autophagy in Human Breast Cancer Cells. Front. Oncol. 2022, 12, 911615. [Google Scholar] [CrossRef] [PubMed]
- Ishida, Y.; Yamasaki, M.; Yukizaki, C.; Nishiyama, K.; Tsubouchi, H.; Okayama, A.; Kataoka, H. Carnosol, rosemary ingredient, induces apoptosis in adult T-cell leukemia/lymphoma cells via glutathione depletion: Proteomic approach using fluorescent two-dimensional differential gel electrophoresis. Hum. Cell 2014, 27, 68–77. [Google Scholar] [CrossRef] [PubMed]
- Tong, L.; Wu, S. The Mechanisms of Carnosol in Chemoprevention of Ultraviolet B-Light-Induced Non-Melanoma Skin Cancer Formation. Sci. Rep. 2018, 8, 3574. [Google Scholar] [CrossRef] [PubMed]
- O’Neill, E.J.; Den Hartogh, D.J.; Azizi, K.; Tsiani, E. Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence. Antioxidants 2020, 9, 961. [Google Scholar] [CrossRef]
- Catanzaro, E.; Canistro, D.; Pellicioni, V.; Vivarelli, F.; Fimognari, C. Anticancer potential of allicin: A review. Pharmacol. Res. 2022, 177, 106118. [Google Scholar] [CrossRef]
- Akkol, E.K.; Tatlı, I.I.; Karatoprak, G.Ş.; Ağar, O.T.; Yücel, Ç.; Sobarzo-Sánchez, E.; Capasso, R. Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin. Cancers 2021, 13, 2733. [Google Scholar] [CrossRef]
- Dey, D.; Hasan, M.M.; Biswas, P.; Papadakos, S.P.; Rayan, R.A.; Tasnim, S.; Bilal, M.; Islam, M.J.; Arshe, F.A.; Arshad, E.M.; et al. Investigating the Anticancer Potential of Salvicine as a Modulator of Topoisomerase II and ROS Signaling Cascade. Front. Oncol. 2022, 12, 899009. [Google Scholar] [CrossRef]
- Tiwari, A.; Mahadik, K.R.; Gabhe, S.Y. Piperine: A comprehensive review of methods of isolation, purification, and biological properties. Med. Drug Discov. 2020, 7, 100027. [Google Scholar] [CrossRef]
- Mitra, S.; Anand, U.; Jha, N.K.; Shekhawat, M.S.; Saha, S.C.; Nongdam, P.; Rengasamy, K.R.R.; Proćków, J.; Dey, A. Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives. Front. Pharmacol. 2022, 12, 772418. [Google Scholar] [CrossRef]
- Wu, Y.-H.; Wu, Y.-R.; Li, B.; Yan, Z.-Y. Cryptotanshinone: A review of its pharmacology activities and molecular mechanisms. Fitoterapia 2020, 145, 104633. [Google Scholar] [CrossRef]
- Somwar, R.; Shum, D.; Djaballah, H.; Varmus, H. Identification and Preliminary Characterization of Novel Small Molecules That Inhibit Growth of Human Lung Adenocarcinoma Cells. SLAS Discov. 2009, 14, 1176–1184. [Google Scholar] [CrossRef]
- Somwar, R.; Erdjument-Bromage, H.; Larsson, E.; Shum, D.; Lockwood, W.W.; Yang, G.; Sander, C.; Ouerfelli, O.; Tempst, P.J.; Djaballah, H.; et al. Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines. Proc. Natl. Acad. Sci. USA 2011, 108, 16375–16380. [Google Scholar] [CrossRef]
- Papa, L.; Hahn, M.; Marsh, E.L.; Evans, B.S.; Germain, D. SOD2 to SOD1 Switch in Breast Cancer. J. Biol. Chem. 2014, 289, 5412–5416. [Google Scholar] [CrossRef]
- Sajesh, B.V.; McManus, K.J. Targeting SOD1 induces synthetic lethal killing in BLM- and CHEK2-deficient colorectal cancer cells. Oncotarget 2015, 6, 27907–27922. [Google Scholar] [CrossRef]
- McAndrew, E.N.; Lepage, C.C.; McManus, K.J. The synthetic lethal killing of RAD54B-deficient colorectal cancer cells by PARP1 inhibition is enhanced with SOD1 inhibition. Oncotarget 2016, 7, 87417–87430. [Google Scholar] [CrossRef]
- Du, T.; Song, Y.; Ray, A.; Chauhan, D.; Anderson, K.C. Proteomic analysis identifies mechanism(s) of overcoming bortezomib resistance via targeting ubiquitin receptor Rpn13. Leukemia 2021, 35, 550–561. [Google Scholar] [CrossRef]
- Ling, M.; Liu, Q.; Wang, Y.; Liu, X.; Jiang, M.; Hu, J. LCS-1 inhibition of superoxide dismutase 1 induces ROS-dependent death of glioma cells and degradates PARP and BRCA1. Front. Oncol. 2022, 12, 937444. [Google Scholar] [CrossRef]
- Gupta, A.; Ahmad, A.; Singh, H.; Kaur, S.; Neethu, K.M.; Ansari, M.M.; Jayamurugan, G.; Khan, R. Nanocarrier Composed of Magnetite Core Coated with Three Polymeric Shells Mediates LCS-1 Delivery for Synthetic Lethal Therapy of BLM-Defective Colorectal Cancer Cells. Biomacromolecules 2018, 19, 803–815. [Google Scholar] [CrossRef]
- Hultsch, S.; Kankainen, M.; Paavolainen, L.; Kovanen, R.-M.; Ikonen, E.; Kangaspeska, S.; Pietiäinen, V.; Kallioniemi, O. Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer 2018, 18, 850. [Google Scholar] [CrossRef]
- Bie, Q.; Dong, H.; Jin, C.; Zhang, H.; Zhang, B. 15d-PGJ2 is a new hope for controlling tumor growth. Am. J. Transl. Res. 2018, 10, 648–658. [Google Scholar] [PubMed]
- Li, J.; Guo, C.; Wu, J. 15-Deoxy-∆-12,14-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-γ: Function and Mechanism. PPAR Res. 2019, 2019, 7242030. [Google Scholar] [CrossRef] [PubMed]
- Cho, W.H.; Choi, C.H.; Park, J.Y.; Kang, S.K.; Kim, Y.K. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) Induces Cell Death Through Caspase-independent Mechanism in A172 Human Glioma Cells. Neurochem. Res. 2006, 31, 1247–1254. [Google Scholar] [CrossRef] [PubMed]
- Su, R.-Y.; Chi, K.-H.; Huang, D.-Y.; Tai, M.-H.; Lin, W.-W. 15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: Involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription. Mol. Cancer Ther. 2008, 7, 3429–3440. [Google Scholar] [CrossRef] [PubMed]
- Shin, S.-W.; Seo, C.-Y.; Han, H.; Han, J.-Y.; Jeong, J.-S.; Kwak, J.-Y.; Park, J.-I. 15d-PGJ2 Induces Apoptosis by Reactive Oxygen Species–mediated Inactivation of Akt in Leukemia and Colorectal Cancer Cells and Shows In vivo Antitumor Activity. Clin. Cancer Res. 2009, 15, 5414–5425. [Google Scholar] [CrossRef]
- Dionne, S.; Levy, E.; Levesque, D.; Seidman, E.G. PPARgamma ligand 15-deoxy-delta 12,14-prostaglandin J2 sensitizes human colon carcinoma cells to TWEAK-induced apoptosis. Anticancer Res. 2010, 30, 157–166. [Google Scholar]
- Wang, J.-J.; Mak, O.-T. Induction of apoptosis by 15d-PGJ2 via ROS formation: An alternative pathway without PPARγ activation in non-small cell lung carcinoma A549 cells. Prostaglandins Other Lipid Mediat. 2011, 94, 104–111. [Google Scholar] [CrossRef]
- Yen, C.-C.; Hsiao, C.-D.; Chen, W.-M.; Wen, Y.-S.; Lin, Y.-C.; Chang, T.-W.; Yao, F.-Y.; Hung, S.-C.; Wang, J.-Y.; Chiu, J.-H.; et al. Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition. Oncotarget 2014, 5, 716–725. [Google Scholar] [CrossRef]
- Choi, J.-E.; Kim, J.-H.; Song, N.-Y.; Suh, J.; Kim, D.-H.; Kim, S.-J.; Na, H.-K.; Nadas, J.; Dong, Z.; Cha, Y.-N.; et al. 15-Deoxy-Δ12,14-prostaglandin J 2 stabilizes hypoxia inducible factor-1α through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2. Free Radic. Res. 2016, 50, 1140–1152. [Google Scholar] [CrossRef]
- Kim, H.-R.; Lee, H.-N.; Lim, K.; Surh, Y.-J.; Na, H.-K. 15-Deoxy-Δ12,14-prostaglandin J2 induces expression of 15-hydroxyprostaglandin dehydrogenase through Elk-1 activation in human breast cancer MDA-MB-231 cells. Mutat. Res. Mol. Mech. Mutagen. 2014, 768, 6–15. [Google Scholar] [CrossRef]
- Na, H.-K.; Yang, H.; Surh, Y.-J. 15-Deoxy-Δ12,14 -prostaglandin J 2 Induces Apoptosis in Ha-ras-transformed Human Breast Epithelial Cells by Targeting IκB kinase–NF-κB Signaling. J. Cancer Prev. 2020, 25, 100–110. [Google Scholar] [CrossRef]
- Kim, D.-H.; Kim, J.-H.; Kim, E.-H.; Na, H.-K.; Cha, Y.-N.; Chung, J.H.; Surh, Y.-J. 15-Deoxy-Δ12,14-prostaglandin J2 upregulates the expression of heme oxygenase-1 and subsequently matrix metalloproteinase-1 in human breast cancer cells: Possible roles of iron and ROS. Carcinogenesis 2009, 30, 645–654. [Google Scholar] [CrossRef]
- Kim, E.-H.; Surh, Y.-J. 15-Deoxy-Δ12,14-prostaglandin J2 as a potential endogenous regulator of redox-sensitive transcription factors. Biochem. Pharmacol. 2006, 72, 1516–1528. [Google Scholar] [CrossRef]
- Xie, J.; Liu, J.; Zhao, M.; Li, X.; Wang, Y.; Zhao, Y.; Cao, H.; Ji, M.; Chen, M.; Hou, P. Disulfiram/Cu Kills and Sensitizes BRAF-Mutant Thyroid Cancer Cells to BRAF Kinase Inhibitor by ROS-Dependently Relieving Feedback Activation of MAPK/ERK and PI3K/AKT Pathways. Int. J. Mol. Sci. 2023, 24, 3418. [Google Scholar] [CrossRef]
- Yip, N.C.; Fombon, I.S.; Liu, P.; Brown, S.; Kannappan, V.; Armesilla, A.L.; Xu, B.; Cassidy, J.; Darling, J.L.; Wang, W. Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. Br. J. Cancer 2011, 104, 1564–1574. [Google Scholar] [CrossRef]
- Hassani, S.; Ghaffari, P.; Chahardouli, B.; Alimoghaddam, K.; Ghavamzadeh, A.; Alizadeh, S.; Ghaffari, S.H. Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes. Biomed. Pharmacother. Biomedecine Pharmacother. 2018, 99, 561–569. [Google Scholar] [CrossRef]
- Liu, Y.; Guan, X.; Wang, M.; Wang, N.; Chen, Y.; Li, B.; Xu, Z.; Fu, F.; Du, C.; Zheng, Z. Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways. Bioengineered 2022, 13, 6579–6589. [Google Scholar] [CrossRef]
- Iljin, K.; Ketola, K.; Vainio, P.; Halonen, P.; Kohonen, P.; Fey, V.; Grafström, R.C.; Perälä, M.; Kallioniemi, O. High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2009, 15, 6070–6078. [Google Scholar] [CrossRef]
- Chen, D.; Cui, Q.C.; Yang, H.; Dou, Q.P. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006, 66, 10425–10433. [Google Scholar] [CrossRef]
- Zha, J.; Chen, F.; Dong, H.; Shi, P.; Yao, Y.; Zhang, Y.; Li, R.; Wang, S.; Li, P.; Wang, W.; et al. Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition. J. Transl. Med. 2014, 12, 163. [Google Scholar] [CrossRef]
- Zhang, X.; Frezza, M.; Milacic, V.; Ronconi, L.; Fan, Y.; Bi, C.; Fregona, D.; Dou, Q.P. Inhibition of tumor proteasome activity by gold-dithiocarbamato complexes via both redox-dependent and -independent processes. J. Cell. Biochem. 2010, 109, 162–172. [Google Scholar] [CrossRef] [PubMed]
- Juarez, J.C.; Betancourt, O.; Pirie-Shepherd, S.R.; Guan, X.; Price, M.L.; Shaw, D.E.; Mazar, A.P.; Doñate, F. Copper Binding by Tetrathiomolybdate Attenuates Angiogenesis and Tumor Cell Proliferation through the Inhibition of Superoxide Dismutase 1. Clin. Cancer Res. 2006, 12, 4974–4982. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Fang, M.; Xu, Z.; Li, X. Tetrathiomolybdate as an old drug in a new use: As a chemotherapeutic sensitizer for non-small cell lung cancer. J. Inorg. Biochem. 2022, 233, 111865. [Google Scholar] [CrossRef] [PubMed]
- Ryumon, S.; Okui, T.; Kunisada, Y.; Kishimoto, K.; Shimo, T.; Hasegawa, K.; Ibaragi, S.; Akiyama, K.; Thu Ha, N.; Monsur Hassan, N.; et al. Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. Oncol. Rep. 2019, 42, 2611–2621. [Google Scholar] [CrossRef] [PubMed]
- Prieto-Bermejo, R.; Romo-González, M.; Pérez-Fernández, A.; Ijurko, C.; Hernández-Hernández, Á. Reactive oxygen species in haematopoiesis: Leukaemic cells take a walk on the wild side. J. Exp. Clin. Cancer Res. 2018, 37, 125. [Google Scholar] [CrossRef]
- Visagie, M.H.; Joubert, A.M. In vitro effects of 2-methoxyestradiol-bis-sulphamate on reactive oxygen species and possible apoptosis induction in a breast adenocarcinoma cell line. Cancer Cell Int. 2011, 11, 43. [Google Scholar] [CrossRef]
- Zhang, Q.; Ma, Y.; Cheng, Y.-F.; Li, W.-J.; Zhang, Z.; Chen, S. Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells. Cancer Lett. 2011, 313, 201–210. [Google Scholar] [CrossRef]
- Gorska, M.; Kuban-Jankowska, A.; Zmijewski, M.; Gammazza, A.M.; Cappello, F.; Wnuk, M.; Gorzynik, M.; Rzeszutek, I.; Daca, A.; Lewinska, A.; et al. DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol. Oncotarget 2015, 6, 15449–15463. [Google Scholar] [CrossRef]
- Bastian, P.E.; Daca, A.; Płoska, A.; Kuban-Jankowska, A.; Kalinowski, L.; Gorska-Ponikowska, M. 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins. Antioxidants 2022, 11, 2013. [Google Scholar] [CrossRef]
- Visagie, M.H.; van den Bout, I.; Joubert, A.M. A bis-sulphamoylated estradiol derivative induces ROS-dependent cell cycle abnormalities and subsequent apoptosis. PLoS ONE 2017, 12, e0176006. [Google Scholar] [CrossRef]
- Lebelo, M.T.; Joubert, A.M.; Visagie, M.H. Sulphamoylated Estradiol Analogue Induces Reactive Oxygen Species Generation to Exert Its Antiproliferative Activity in Breast Cancer Cell Lines. Molecules 2020, 25, 4337. [Google Scholar] [CrossRef]
- Borahay, M.A.; Vincent, K.L.; Motamedi, M.; Tekedereli, I.; Salama, S.A.; Ozpolat, B.; Kilic, G.S. Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model. Reprod. Sci. 2021, 28, 271–277. [Google Scholar] [CrossRef]
- Al-Qahtani, S.D.; Bin-Melaih, H.H.; Atiya, E.M.; Fahmy, U.A.; Binmahfouz, L.S.; Neamatallah, T.; Al-Abbasi, F.A.; Abdel-Naim, A.B. Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells. Life 2022, 12, 1369. [Google Scholar] [CrossRef]
- Tomeh, M.; Hadianamrei, R.; Zhao, X. A Review of Curcumin and Its Derivatives as Anticancer Agents. Int. J. Mol. Sci. 2019, 20, 1033. [Google Scholar] [CrossRef]
- Sánchez, Y.; Simón, G.P.; Calviño, E.; de Blas, E.; Aller, P. Curcumin Stimulates Reactive Oxygen Species Production and Potentiates Apoptosis Induction by the Antitumor Drugs Arsenic Trioxide and Lonidamine in Human Myeloid Leukemia Cell Lines. J. Pharmacol. Exp. Ther. 2010, 335, 114–123. [Google Scholar] [CrossRef]
- Larasati, Y.A.; Yoneda-Kato, N.; Nakamae, I.; Yokoyama, T.; Meiyanto, E.; Kato, J. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci. Rep. 2018, 8, 2039. [Google Scholar] [CrossRef]
- Chen, M.; Zhou, B.; Zhong, P.; Rajamanickam, V.; Dai, X.; Karvannan, K.; Zhou, H.; Zhang, X.; Liang, G. Increased Intracellular Reactive Oxygen Species Mediates the Anti-Cancer Effects of WZ35 via Activating Mitochondrial Apoptosis Pathway in Prostate Cancer Cells: Targeting ROS Induces Cancer Cell Death. Prostate 2017, 77, 489–504. [Google Scholar] [CrossRef]
- Zhang, X.; Chen, M.; Zou, P.; Kanchana, K.; Weng, Q.; Chen, W.; Zhong, P.; Ji, J.; Zhou, H.; He, L.; et al. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. BMC Cancer 2015, 15, 866. [Google Scholar] [CrossRef]
- Gabr, S.A.; Elsaed, W.M.; Eladl, M.A.; El-Sherbiny, M.; Ebrahim, H.A.; Asseri, S.M.; Eltahir, Y.A.M.; Elsherbiny, N.; Eldesoqui, M. Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines. Life 2022, 12, 1427. [Google Scholar] [CrossRef]
- Wang, H.; Xu, Y.; Sun, J.; Sui, Z. The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production. Front. Oncol. 2021, 11, 644197. [Google Scholar] [CrossRef]
- Zou, P.; Zhang, J.; Xia, Y.; Kanchana, K.; Guo, G.; Chen, W.; Huang, Y.; Wang, Z.; Yang, S.; Liang, G. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer. Oncotarget 2015, 6, 5860–5876. [Google Scholar] [CrossRef] [PubMed]
- Lin, X.; Wang, L.; Zhao, L.; Zhu, Z.; Chen, T.; Chen, S.; Tao, Y.; Zeng, T.; Zhong, Y.; Sun, H.; et al. Curcumin micelles suppress gastric tumor cell growth by upregulating ROS generation, disrupting redox equilibrium and affecting mitochondrial bioenergetics. Food Funct. 2020, 11, 4146–4159. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.-T.; Huang, A.-C.; Tang, N.-Y.; Liu, H.-C.; Liao, C.-L.; Ji, B.-C.; Chou, Y.-C.; Yang, M.-D.; Lu, H.-F.; Chung, J.-G. Bisdemethoxycurcumin-induced S phase arrest through the inhibition of cyclin A and E and induction of apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathways in human lung cancer NCI H460 cells: Bisdemethoxycurcumin-induced apoptosis in nci-h460 cells. Environ. Toxicol. 2016, 31, 1899–1908. [Google Scholar] [CrossRef] [PubMed]
- Luo, S.-M.; Wu, Y.-P.; Huang, L.-C.; Huang, S.-M.; Hueng, D.-Y. The Anti-Cancer Effect of Four Curcumin Analogues on Human Glioma Cells. OncoTargets Ther. 2021, 14, 4345–4359. [Google Scholar] [CrossRef]
- Chen, M.; Qian, C.; Jin, B.; Hu, C.; Zhang, L.; Wang, M.; Zhou, B.; Zuo, W.; Huang, L.; Wang, Y. Curcumin analog WZ26 induces ROS and cell death via inhibition of STAT3 in cholangiocarcinoma. Cancer Biol. Ther. 2023, 24, 2162807. [Google Scholar] [CrossRef]
- Perrone, D.; Ardito, F.; Giannatempo, G.; Dioguardi, M.; Troiano, G.; Lo Russo, L.; De Lillo, A.; Laino, L.; Lo Muzio, L. Biological and therapeutic activities, and anticancer properties of curcumin. Exp. Ther. Med. 2015, 10, 1615–1623. [Google Scholar] [CrossRef]
- Gallego-Jara, J.; Lozano-Terol, G.; Sola-Martínez, R.A.; Cánovas-Díaz, M.; De Diego Puente, T. A Compressive Review about Taxol®: History and Future Challenges. Molecules 2020, 25, 5986. [Google Scholar] [CrossRef]
- Li, M.; Yin, L.; Wu, L.; Zhu, Y.; Wang, X. Paclitaxel inhibits proliferation and promotes apoptosis through regulation ROS and endoplasmic reticulum stress in osteosarcoma cell. Mol. Cell. Toxicol. 2020, 16, 377–384. [Google Scholar] [CrossRef]
- Zhang, Y.; Tang, Y.; Tang, X.; Wang, Y.; Zhang, Z.; Yang, H. Paclitaxel Induces the Apoptosis of Prostate Cancer Cells via ROS-Mediated HIF-1α Expression. Molecules 2022, 27, 7183. [Google Scholar] [CrossRef]
- Mohiuddin, M.; Kasahara, K. Paclitaxel Impedes EGFR-mutated PC9 Cell Growth via Reactive Oxygen Species-mediated DNA Damage and EGFR/PI3K/AKT/mTOR Signaling Pathway Suppression. Cancer Genom. Proteom. 2021, 18, 645–659. [Google Scholar] [CrossRef]
- Hao, X.; Bu, W.; Lv, G.; Xu, L.; Hou, D.; Wang, J.; Liu, X.; Yang, T.; Zhang, X.; Liu, Q.; et al. Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress. Oncogene 2022, 41, 427–443. [Google Scholar] [CrossRef]
- Kim, S.J.; Kim, H.S.; Seo, Y.R. Understanding of ROS-Inducing Strategy in Anticancer Therapy. Oxid. Med. Cell. Longev. 2019, 2019, 5381692. [Google Scholar] [CrossRef]
- Mirzaei, S.; Hushmandi, K.; Zabolian, A.; Saleki, H.; Torabi, S.M.R.; Ranjbar, A.; SeyedSaleh, S.; Sharifzadeh, S.O.; Khan, H.; Ashrafizadeh, M.; et al. Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies. Molecules 2021, 26, 2382. [Google Scholar] [CrossRef]
- Marullo, R.; Werner, E.; Degtyareva, N.; Moore, B.; Altavilla, G.; Ramalingam, S.S.; Doetsch, P.W. Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions. PLoS ONE 2013, 8, e81162. [Google Scholar] [CrossRef]
- Choi, Y.-M.; Kim, H.-K.; Shim, W.; Anwar, M.A.; Kwon, J.-W.; Kwon, H.-K.; Kim, H.J.; Jeong, H.; Kim, H.M.; Hwang, D.; et al. Mechanism of Cisplatin-Induced Cytotoxicity Is Correlated to Impaired Metabolism Due to Mitochondrial ROS Generation. PLoS ONE 2015, 10, e0135083. [Google Scholar] [CrossRef]
- Kleih, M.; Böpple, K.; Dong, M.; Gaißler, A.; Heine, S.; Olayioye, M.A.; Aulitzky, W.E.; Essmann, F. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019, 10, 851. [Google Scholar] [CrossRef]
- Magnano, S.; Hannon Barroeta, P.; Duffy, R.; O’Sullivan, J.; Zisterer, D.M. Cisplatin induces autophagy-associated apoptosis in human oral squamous cell carcinoma (OSCC) mediated in part through reactive oxygen species. Toxicol. Appl. Pharmacol. 2021, 427, 115646. [Google Scholar] [CrossRef]
- Yu, W.; Chen, Y.; Dubrulle, J.; Stossi, F.; Putluri, V.; Sreekumar, A.; Putluri, N.; Baluya, D.; Lai, S.Y.; Sandulache, V.C. Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism. Sci. Rep. 2018, 8, 4306. [Google Scholar] [CrossRef]
- Sritharan, S.; Sivalingam, N. A comprehensive review on time-tested anticancer drug doxorubicin. Life Sci. 2021, 278, 119527. [Google Scholar] [CrossRef]
- Thorn, C.F.; Oshiro, C.; Marsh, S.; Hernandez-Boussard, T.; McLeod, H.; Klein, T.E.; Altman, R.B. Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenet. Genom. 2011, 21, 440–446. [Google Scholar] [CrossRef]
- Filippova, M.; Filippov, V.; Williams, V.M.; Zhang, K.; Kokoza, A.; Bashkirova, S.; Duerksen-Hughes, P. Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents. BioMed Res. Int. 2014, 2014, 574659. [Google Scholar] [CrossRef] [PubMed]
- Tsang, W.P.; Chau, S.P.Y.; Kong, S.K.; Fung, K.P.; Kwok, T.T. Reactive oxygen species mediate doxorubicin induced p53-independent apoptosis. Life Sci. 2003, 73, 2047–2058. [Google Scholar] [CrossRef] [PubMed]
- Shafei, A.; El-Bakly, W.; Sobhy, A.; Wagdy, O.; Reda, A.; Aboelenin, O.; Marzouk, A.; El Habak, K.; Mostafa, R.; Ali, M.A.; et al. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed. Pharmacother. 2017, 95, 1209–1218. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, M.P.; Pham, D.P.; Kim, D. Oxidative Stress-Induced Silver Nano-Carriers for Chemotherapy. Pharmaceuticals 2022, 15, 1449. [Google Scholar] [CrossRef]
- Hernandes, E.P.; Lazarin-Bidóia, D.; Bini, R.D.; Nakamura, C.V.; Cótica, L.F.; de Oliveira Silva Lautenschlager, S. Doxorubicin-Loaded Iron Oxide Nanoparticles Induce Oxidative Stress and Cell Cycle Arrest in Breast Cancer Cells. Antioxidants 2023, 12, 237. [Google Scholar] [CrossRef]
- Zheng, G.; Zheng, M.; Yang, B.; Fu, H.; Li, Y. Improving breast cancer therapy using doxorubicin loaded solid lipid nanoparticles: Synthesis of a novel arginine-glycine-aspartic tripeptide conjugated, pH sensitive lipid and evaluation of the nanomedicine in vitro and in vivo. Biomed. Pharmacother. 2019, 116, 109006. [Google Scholar] [CrossRef]
- Xu, J.; Su, X.; Burley, S.K.; Zheng, X.F.S. Nuclear SOD1 in Growth Control, Oxidative Stress Response, Amyotrophic Lateral Sclerosis, and Cancer. Antioxidants 2022, 11, 427. [Google Scholar] [CrossRef]
- Hu, Y.; Lin, Q.; Zhao, H.; Li, X.; Sang, S.; McClements, D.J.; Long, J.; Jin, Z.; Wang, J.; Qiu, C. Bioaccessibility and bioavailability of phytochemicals: Influencing factors, improvements, and evaluations. Food Hydrocoll. 2023, 135, 108165. [Google Scholar] [CrossRef]
- Cheng, Z.; Li, M.; Dey, R.; Chen, Y. Nanomaterials for cancer therapy: Current progress and perspectives. J. Hematol. Oncol. 2021, 14, 85. [Google Scholar] [CrossRef]
- Luo, M.; Zhou, L.; Huang, Z.; Li, B.; Nice, E.C.; Xu, J.; Huang, C. Antioxidant Therapy in Cancer: Rationale and Progress. Antioxidants 2022, 11, 1128. [Google Scholar] [CrossRef]
Phytochemical | Chemical Class | Plant Source | Cancer Types | Mechanisms Downstream of ROS Induction | Refs |
---|---|---|---|---|---|
Allicin | Thiosulfinate | Allium sativum (garlic) | Hepatocellular, lung, | Mitochondria-dependent apoptotic cell death | [96] |
Hepatocellular | Mitochondrial membrane depolarization | ||||
Lung, leukemia | G2/M cell cycle arrest | ||||
Emodin | Anthraquinone | Rheum palmatum (Chinese rhubarb) | Lung, breast, colon, cervical, prostate, oral squamous cell | Mitochondria-dependent apoptotic cell death | [97] |
Lung, hepatocellular, colon, cervical | Mitochondrial membrane depolarization | ||||
Hepatocellular, breast, gastric, colon, cervical | G0/G1 cell cycle arrest | ||||
Gastric, colon, lung | G2/M cell cycle arrest | ||||
Hepatocellular | ↑ Cyclophilin D expression | ||||
Pancreatic, gall bladder, ovarian | ↓ Survivin expression | ||||
Oral squamous cell | ER stress | ||||
Cervical, lung, breast, oral squamous cell | Oxidative DNA damage | ||||
Salvicine | Diterpenoid quinone | Salvia prionitis | Leukemia, breast | Oxidative DNA damage | [98] |
Piperine | Alkaloid | Piper nigrum (black pepper) Piper longum (long pepper) | Prostate, cervical, oral squamous cell, rectal, breast, ovarian | Mitochondria-dependent apoptotic cell death | [99,100] |
Oral squamous cell, breast | Mitochondrial membrane depolarization | ||||
Rectal | G0/G1 cell cycle arrest | ||||
Oral squamous cell | G2/M cell cycle arrest | ||||
Cryptotanshinone | Abietane diterpenoid | Salvia miltiorrhiza (Chinese sage) Salvia przewalskii (red sage) | Breast | ↓ Survivin expression | [101] |
Gastric | Inhibition of AKT pathway | ||||
Colon | Inhibition of p38–MAPK–NF-κB signaling pathway | ||||
Gastric | G2/M cell cycle arrest | ||||
Gastric, leukemia, | Mitochondria-dependent apoptotic cell death | ||||
Melanoma, lung | ↑ Death receptor 5 expression | ||||
Hepatocellular, lung, breast, lymphoma, gastric, cervical | ER stress |
Pro-Oxidative Drug | Mechanism of ROS Induction | Cancer | Clinical Trial | ||
---|---|---|---|---|---|
Phase | ID | Status | |||
Choline tetrathiomolybdate (ATN-224) | Inhibition of superoxide dismutase 1 | Breast | II | NCT00674557 | Terminated |
NCT00195091 | Active, not recruiting | ||||
Prostate | II | NCT00150995 | Completed | ||
Non-small cell lung | I | NCT01837329 | Completed | ||
Lung | I | NCT00560495 | Withdrawn | ||
Multiple myeloma | I/II | NCT00352742 | Terminated | ||
Esophageal | II | NCT00176800 | Completed | ||
Colorectal | II | NCT00176774 | Completed | ||
Hepatocellular | II | NCT00006332 | Completed | ||
2-methoxyoestradiol | Unknown | Recurrent glioblastoma multiforme | II | NCT00306618 | Completed |
NCT00481455 | Completed | ||||
Refractory multiple myeloma | I | NCT00028821 | Completed | ||
II | NCT00592579 | Completed | |||
Prostate | II | NCT00394810 | Completed | ||
Ovarian | II | NCT00400348 | Completed | ||
Unspecified adult solid tumor | I | NCT00030095 | Completed | ||
Carcinoid tumor | II | NCT00328497 | Completed | ||
Metastatic renal cell | II | NCT00444314 | Completed | ||
Curcumin * | Inhibition of catalase, superoxide dismutase 1, glyoxalase 1, and NADPH dehydrogenase [quinone] 1 | Prostate | I | NCT04403568 | Withdrawn |
II | NCT03493997 | Completed | |||
III | NCT02064673 | Recruiting | |||
NCT03769766 | Recruiting | ||||
Breast | I | NCT03980509 | Active, not recruiting | ||
II | NCT01042938 | Completed | |||
NCT03072992 | Completed | ||||
Colorectal | I | NCT01859858 | Completed | ||
NCT01294072 | Recruiting | ||||
NCT01333917 | Completed | ||||
II | NCT02439385 | Completed | |||
Pancreatic | I | NCT02336087 | Active, not recruiting | ||
II | NCT00192842 | Completed | |||
Head and neck | I | NCT01160302 | Completed | ||
II | NCT04208334 | Completed | |||
Cervical | I | NCT01035580 | Completed | ||
II | NCT04294836 | Withdrawn | |||
Lung | I/II | NCT01048983 | Withdrawn | ||
II | NCT03598309 | Recruiting | |||
III | NCT04871412 | Recruiting | |||
Leukemia | II | NCT05045443 | Recruiting | ||
NCT02100423 | Completed | ||||
Multiple myeloma | II | NCT04731844 | Recruiting | ||
NCT01269203 | Withdrawn |
Pro-Oxidative Drug | Mechanism of ROS Induction | Cancer | Clinical Trial | ||
---|---|---|---|---|---|
Intervention | Phase | ID | |||
Cisplatin | Mitochondrial DNA damage | Breast | Cisplatin in combination with gemcitabine | II | NCT04297267 |
Cisplatin in combination with veliparib | II | NCT02595905 | |||
Ovarian | Cisplatin in combination with palbociclib | I | NCT02897375 | ||
Lung | Cisplatin in combination with gemcitabine and nadumolimab | I/II | NCT05116891 | ||
Doxorubicin |
| Breast | PLD in combination with and cyclophosphamide | II | NCT01210768 |
PLD in combination with IN10018 | II | NCT05830539 | |||
Hepatocellular | Doxorubicin-eluting beads | I | NCT05093920 | ||
Doxorubicin in combination with sorafenib | II | NCT01840592 | |||
Ovarian | PLD in combination with pembrolizumab and bevacizumab | I | NCT03596281 | ||
PLD in combination with carboplatin | IV | NCT01210768 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 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 (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Nizami, Z.N.; Aburawi, H.E.; Semlali, A.; Muhammad, K.; Iratni, R. Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence. Antioxidants 2023, 12, 1159. https://doi.org/10.3390/antiox12061159
Nizami ZN, Aburawi HE, Semlali A, Muhammad K, Iratni R. Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence. Antioxidants. 2023; 12(6):1159. https://doi.org/10.3390/antiox12061159
Chicago/Turabian StyleNizami, Zohra Nausheen, Hanan E. Aburawi, Abdelhabib Semlali, Khalid Muhammad, and Rabah Iratni. 2023. "Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence" Antioxidants 12, no. 6: 1159. https://doi.org/10.3390/antiox12061159