Contradictory roles of Nrf2/Keap1 signaling pathway in cancer prevention/promotion and chemoresistance

Loignon, 2009, Cul3 overexpression depletes Nrf2 in breast cancer and is associated with sensitivity to carcinogens, to oxidative stress, and to chemotherapy, Mol. Cancer Ther., 8, 2432, 10.1158/1535-7163.MCT-08-1186 Siegel, 2000, Immunodetection of NAD (P) H: quinone oxidoreductase 1 (NQO1) in human tissues, Free Radic. Biol. Med., 29, 246, 10.1016/S0891-5849(00)00310-5 Basu, 2004, Immunohistochemical analysis of NAD (P) H: quinone oxidoreductase and NADPH cytochrome P450 reductase in human superficial bladder tumours: relationship between tumour enzymology and clinical outcome following intravesical mitomycin C therapy, Int. J. Cancer, 109, 703, 10.1002/ijc.20005 Homma, 2009, Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer, Clin. Cancer Res., 15, 3423, 10.1158/1078-0432.CCR-08-2822 Mishra, 2014, Epigenetic modifications of keap1 regulate its interaction with the protective factor Nrf2 in the development of diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 55, 7256, 10.1167/iovs.14-15193 Villeneuve, 2010, Regulation of the Nrf2–Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases, Antioxid. Redox Signal., 13, 1699, 10.1089/ars.2010.3211 Jaramillo, 2013, The emerging role of the Nrf2–Keap1 signaling pathway in cancer, Genes Dev., 27, 2179, 10.1101/gad.225680.113 Shelton, 2013, The transcription factor NF-E2-related factor 2 (Nrf2): a protooncogene?, FASEB J., 27, 414, 10.1096/fj.12-217257 Taguchi, 2011, Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution, Genes Cells, 16, 123, 10.1111/j.1365-2443.2010.01473.x Schafer, 2010, Nrf2: a central regulator of UV protection in the epidermis, Cell Cycle, 9, 2917, 10.4161/cc.9.15.12701 Beyer, 2008, The cytoprotective Nrf2 transcription factor controls insulin receptor signaling in the regenerating liver, Cell Cycle, 7, 874, 10.4161/cc.7.7.5617 Beyer, 2008, Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance, EMBO J., 27, 212, 10.1038/sj.emboj.7601950 Brigelius-Flohé, 2012, The yin and yang of nrf2-regulated selenoproteins in carcinogenesis, Int. J. Cell Biol., 2012, 10.1155/2012/486147 Eades, 2011, miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells, J. Biol. Chem., 286, 40725, 10.1074/jbc.M111.275495 Yokoo, 2016, Effects of Nrf2 silencing on oxidative stress-associated intestinal carcinogenesis in mice, Cancer Med., 10.1002/cam4.672 Iida, 2004, Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis, Cancer Res., 64, 6424, 10.1158/0008-5472.CAN-04-1906 Khor, 2008, Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer, Cancer Prevent. Res., 1, 187, 10.1158/1940-6207.CAPR-08-0028 Zhang, 2010, Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth, Mol. Cancer Ther., 9, 336, 10.1158/1535-7163.MCT-09-0589 Leinonen, 2015, Dysregulation of the Keap1–Nrf2 pathway in cancer, Biochem. Soc. Trans., 43, 645, 10.1042/BST20150048 Rushworth, 2011, High basal nuclear levels of Nrf2 in acute myeloid leukemia reduces sensitivity to proteasome inhibitors, Cancer Res., 71, 1999, 10.1158/0008-5472.CAN-10-3018 Pietsch, 2003, Nrf2 mediates the induction of ferritin H in response to xenobiotics and cancer chemopreventive dithiolethiones, J. Biol. Chem., 278, 2361, 10.1074/jbc.M210664200 Kim, 2008, Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells, Free Radic. Biol. Med., 45, 537, 10.1016/j.freeradbiomed.2008.05.011 Akhdar, 2009, Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells, Eur. J. Cancer, 45, 2219, 10.1016/j.ejca.2009.05.017 Giudice, 2006, Activation of the Nrf2–ARE signaling pathway: a promising strategy in cancer prevention, Bioessays, 28, 169, 10.1002/bies.20359 Kwak, 2010, Targeting NRF2 signaling for cancer chemoprevention, Toxicology and applied pharmacology, 244, 66, 10.1016/j.taap.2009.08.028 Hayes, 2010, Cancer chemoprevention mechanisms mediated through the Keap1–Nrf2 pathway, Antioxid. Redox Signal., 13, 1713, 10.1089/ars.2010.3221 Slocum, 2011, Nrf2: control of sensitivity to carcinogens, Arch. Toxicol., 85, 273, 10.1007/s00204-011-0675-4 Chan, 1996, NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development, Proc. Natl. Acad. Sci. U. S. A., 93, 13943, 10.1073/pnas.93.24.13943 Geismann, 2014, Cytoprotection “gone astray”: Nrf2 and its role in cancer, OncoTargets Ther., 7, 1497 McMahon, 2001, The Cap ‘n’ Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes, Cancer Res., 61, 3299 Hayes, 2000, The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin, Biochem. Soc. Trans., 28, 33, 10.1042/bst0280033 Chanas, 2002, Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice, Biochem. J., 365, 405, 10.1042/bj20020320 Chan, 2000, Impaired expression of glutathione synthetic enzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein, Biochim. Biophys. Acta: Gene Struct. Expr., 1517, 19, 10.1016/S0167-4781(00)00238-4 Kwak, 2001, Role of transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H-1, 2-dimethiole-3-thione, Mol. Med., 7, 135, 10.1007/BF03401947 Schultz, 2014, Nrf1 and nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells, PLOS ONE, 9, e87204, 10.1371/journal.pone.0087204 Venugopal, 1996, Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD (P) H: quinone oxidoreductase1 gene, Proc. Natl. Acad. Sci. U. S. A., 93, 14960, 10.1073/pnas.93.25.14960 Kou, 2013, Natural products for cancer prevention associated with Nrf2–ARE pathway, Food Sci. Hum. Wellness, 2, 22, 10.1016/j.fshw.2013.01.001 Khor, 2011, Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation, Biochem. Pharmacol., 82, 1073, 10.1016/j.bcp.2011.07.065 Kumar, 2014, Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases, Nat. Prod. Rep., 31, 109, 10.1039/C3NP70065H Lau, 2008, Dual roles of Nrf2 in cancer, Pharmacol. Res., 58, 262, 10.1016/j.phrs.2008.09.003 Geismann, 2014, Cytoprotection “gone astray”: Nrf2 and its role in cancer, Onco Targets Ther., 7, 1497 Ramos-Gomez, 2003, Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene–DNA adducts and tumor yield in mice, Carcinogenesis, 24, 461, 10.1093/carcin/24.3.461 Yates, 2006, Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole, Cancer Res., 66, 2488, 10.1158/0008-5472.CAN-05-3823 Satoh, 2010, Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung, Carcinogenesis, 31, 1833, 10.1093/carcin/bgq105 Menegon, 2016, The dual roles of NRF2 in cancer, Trends Mol. Med., 10.1016/j.molmed.2016.05.002 Ikeda, 2004, Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis, Biochem. J., 380, 515, 10.1042/bj20031948 Sporn, 2012, NRF2 and cancer: the good, the bad and the importance of context, Nat. Rev. Cancer, 12, 564, 10.1038/nrc3278 Gañán-Gómez, 2013, Oncogenic functions of the transcription factor Nrf2, Free Radic. Biol. Med., 65, 750, 10.1016/j.freeradbiomed.2013.06.041 Lister, 2011, Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy, Mol. Cancer, 10, 37, 10.1186/1476-4598-10-37 Chen, 2010, Nrf2 expression in endometrial serous carcinomas and its precancers, Int. J. Clin. Exp. Pathol., 4, 85 Yoo, 2012, Somatic mutations of the KEAP1 gene in common solid cancers, Histopathology, 60, 943, 10.1111/j.1365-2559.2012.04178.x Lei, 2016, Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma, BMC Cancer, 16, 410, 10.1186/s12885-016-2462-3 Shibata, 2008, Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy, Proc. Natl. Acad. Sci. U. S. A., 105, 13568, 10.1073/pnas.0806268105 Bryan, 2013, The Nrf2 cell defence pathway: Keap1-dependent and-independent mechanisms of regulation, Biochem. Pharmacol., 85, 705, 10.1016/j.bcp.2012.11.016 Solis, 2010, Nrf2 and Keap1 abnormalities in non–small cell lung carcinoma and association with clinicopathologic features, Clin. Cancer Res., 16, 3743, 10.1158/1078-0432.CCR-09-3352 Wang, 2008, Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues, Biochem. Biophys. Res. Commun., 373, 151, 10.1016/j.bbrc.2008.06.004 Hanada, 2012, Methylation of the KEAP1 gene promoter region in human colorectal cancer, BMC Cancer, 12, 66, 10.1186/1471-2407-12-66 Barbano, 2013, Aberrant Keap1 methylation in breast cancer and association with clinicopathological features, Epigenetics, 8, 105, 10.4161/epi.23319 Van Jaarsveld, 2013, miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells, Oncogene, 32, 4284, 10.1038/onc.2012.433 Yang, 2011, MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism, Breast Cancer Res. Treat., 129, 983, 10.1007/s10549-011-1604-1 Yamamoto, 2014, The impact of miRNA-based molecular diagnostics and treatment of NRF2-stabilized tumors, Mol. Cancer Res., 12, 58, 10.1158/1541-7786.MCR-13-0246-T Kinch, 2011, Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2, Cancer Cell, 20, 418, 10.1016/j.ccr.2011.10.005 Ramos, 2015, Mechanism-based cancer therapy: resistance to therapy, therapy for resistance, Oncogene, 34, 3617, 10.1038/onc.2014.314 Szakács, 2006, Targeting multidrug resistance in cancer, Nat. Rev. Drug Discov., 5, 219, 10.1038/nrd1984 Tew, 1994, Glutathione-associated enzymes in anticancer drug resistance, Cancer Res., 54, 4313 Wosikowski, 1997, Altered gene expression in drug-resistant human breast cancer cells, Clin. Cancer Res., 3, 2405 Rosell, 2004, Molecular predictors of response to chemotherapy in lung cancer O’Connor, 1997, Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents, Cancer Res., 57, 4285 Borek, 2004, Antioxidants and radiation therapy, J. Nutr., 134, 3207S, 10.1093/jn/134.11.3207S Zhivotovsky, 1999, Tumor radiosensitivity and apoptosis, Exp. Cell Res., 248, 10, 10.1006/excr.1999.4452 Lee, 2003, Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis, J. Biol. Chem., 278, 12029, 10.1074/jbc.M211558200 Smith, 2008, In vitro evaluation of the effects of gefitinib on the modulation of cytotoxic activity of selected anticancer agents in a panel of human ovarian cancer cell lines, Cancer Chemother. Pharmacol., 62, 51, 10.1007/s00280-007-0572-y Meijerman, 2008, Combined action and regulation of phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer, Cancer Treat. Rev., 34, 505, 10.1016/j.ctrv.2008.03.002 Lu, 2016, The Keap1–Nrf2–ARE pathway as a potential preventive and therapeutic target: an update, Med. Res. Rev., 10.1002/med.21396 Shibata, 2008, Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer, Gastroenterology, 135, 10.1053/j.gastro.2008.06.082 Wang, 2008, Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2, Carcinogenesis, 29, 1235, 10.1093/carcin/bgn095 Tarumoto, 2004, Ascorbic acid restores sensitivity to imatinib via suppression of Nrf2-dependent gene expression in the imatinib-resistant cell line, Exp. Hematol., 32, 375, 10.1016/j.exphem.2004.01.007 Wang, 2014, Oxaliplatin activates the Keap1/Nrf2 antioxidant system conferring protection against the cytotoxicity of anticancer drugs, Free Radic. Biol. Med., 70, 68, 10.1016/j.freeradbiomed.2014.02.010 Tang, 2011, Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs, Free Radic. Biol. Med., 50, 1599, 10.1016/j.freeradbiomed.2011.03.008 Chian, 2013, Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway, Asian Pac. J. Cancer Prevent., 15, 2911, 10.7314/APJCP.2014.15.6.2911 Sabzichi, 2014, Luteolin-loaded phytosomes sensitize human breast carcinoma MDA-MB 231 cells to doxorubicin by suppressing Nrf2 mediated signalling, Asian Pac. J. Cancer Prevent., 15, 5311, 10.7314/APJCP.2014.15.13.5311 Chian, 2014, Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo, Biochemical and biophysical research communications, 447, 602, 10.1016/j.bbrc.2014.04.039 Verma, 2015, Isoniazid prevents Nrf2 translocation by inhibiting ERK1 phosphorylation and induces oxidative stress and apoptosis, Redox Biol., 6, 80, 10.1016/j.redox.2015.06.020 Wagner, 2011, Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes-role of the redox-regulated transcription factor Nrf2, BMC Complement. Altern. Med., 11, 1, 10.1186/1472-6882-11-1 Valenzuela, 2014, Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells, Br. J. Cancer, 111, 874, 10.1038/bjc.2014.380 Ren, 2011, Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism, Proc. Natl. Acad. Sci. U. S. A., 108, 1433, 10.1073/pnas.1014275108 Olayanju, 2015, Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity—implications for therapeutic targeting of Nrf2, Free Radic. Biol. Med., 78, 202, 10.1016/j.freeradbiomed.2014.11.003 Do, 2014, Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1α/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents, Free Radic. Biol. Med., 74, 21, 10.1016/j.freeradbiomed.2014.06.010 Boesch-Saadatmandi, 2009, Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cells, J. Anim. Physiol. Anim. Nutr., 93, 547, 10.1111/j.1439-0396.2008.00838.x Arlt, 2013, Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity, Oncogene, 32, 4825, 10.1038/onc.2012.493 Zhu, 2016, An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy, Free Radic. Biol. Med., 99, 544, 10.1016/j.freeradbiomed.2016.09.010 MacLeod, 2009, Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1–NRF2 pathway, and not the BACH1–NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds, Carcinogenesis, 30, 1571, 10.1093/carcin/bgp176 Malhotra, 2010, Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis, Nucleic Acids Res., 38, 5718, 10.1093/nar/gkq212 Singh, 2010, Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype, Mol. Cancer Ther., 9, 2365, 10.1158/1535-7163.MCT-10-0108 Wang, 2014, Nrf2 upregulates ATP binding cassette transporter expression and activity at the blood–brain and blood–spinal cord barriers, J. Neurosci., 34, 8585, 10.1523/JNEUROSCI.2935-13.2014 Jozkowicz, 2007, Heme oxygenase-1 in tumors: is it a false friend?, Antioxid. Redox Signal., 9, 2099, 10.1089/ars.2007.1659 Chau, 2015, Heme oxygenase-1: emerging target of cancer therapy, J. Biomed. Sci., 22, 22, 10.1186/s12929-015-0128-0 Ferrando, 2011, Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer, Angiogenesis, 14, 467, 10.1007/s10456-011-9230-4 Hill, 2005, Heme oxygenase-1 inhibits rat and human breast cancer cell proliferation: mutual cross inhibition with indoleamine 2,3-dioxygenase, FASEB J., 19, 1957, 10.1096/fj.05-3875com Chao, 2013, Induction of heme oxygenase-1 and inhibition of TPA-induced matrix metalloproteinase-9 expression by andrographolide in MCF-7 human breast cancer cells, Carcinogenesis, 34, 1843, 10.1093/carcin/bgt131 Was, 2006, Overexpression of heme oxygenase-1 in murine melanoma: increased proliferation and viability of tumor cells, decreased survival of mice, Am. J. Pathol., 169, 2181, 10.2353/ajpath.2006.051365 Loboda, 2008, Janus face of Nrf2–HO-1 axis in cancer—Friend in chemoprevention, foe in anticancer therapy, Lung Cancer, 60, 1, 10.1016/j.lungcan.2007.10.024 Wang, 2010, Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival, J. Surg. Res., 164, e99, 10.1016/j.jss.2010.05.058 Bancos, 2010, Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Δ 12,14-prostaglandin J 2 requires Nrf2, Cell. Immunol., 262, 18, 10.1016/j.cellimm.2009.12.003 Kweon, 2006, Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells contributes to resistance to apoptosis induced by epigallocatechin 3-gallate, J. Biol. Chem., 281, 33761, 10.1074/jbc.M604748200 Brigelius-Flohé, 2008, Selenium compounds and selenoproteins in cancer, Chem. Biodivers., 5, 389, 10.1002/cbdv.200890039 Turanov, 2010, Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets, Biochem. J., 430, 285, 10.1042/BJ20091378 Nguyen, 2006, Thioredoxin reductase as a novel molecular target for cancer therapy, Cancer Lett., 236, 164, 10.1016/j.canlet.2005.04.028 Grogan, 2000, Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival, Hum. Pathol., 31, 475, 10.1053/hp.2000.6546 Raffel, 2003, Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival, J. Lab. Clin. Med., 142, 46, 10.1016/S0022-2143(03)00068-4 Penney, 2013, Thioredoxin-mediated redox regulation of resistance to endocrine therapy in breast cancer, Biochim. Biophys. Acta: Rev. Cancer, 1836, 60 Li, 2012, Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma, Oncotarget, 3, 314, 10.18632/oncotarget.463 Yoo, 2006, Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of lung carcinoma cells, J. Biol. Chem., 281, 13005, 10.1074/jbc.C600012200 Sakurai, 2005, Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: role of NF-E2-related factor-2, J. Cell. Physiol., 203, 529, 10.1002/jcp.20246 Sasada, 1999, Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-diamminedichloroplatinum (II), Free Radic. Biol. Med., 27, 504, 10.1016/S0891-5849(99)00101-X Kim, 2013, Antiproliferative effect of gold (I) compound auranofin through inhibition of STAT3 and telomerase activity in MDA-MB 231 human breast cancer cells, BMB Rep., 46, 59, 10.5483/BMBRep.2013.46.1.123 PArK, 2014, Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53, Int. J. Oncol., 45, 1691, 10.3892/ijo.2014.2579 Fan, 2014, Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo, Cell Death Dis., 5, e1191, 10.1038/cddis.2014.132 Park, 2014, Auranofin promotes mitochondrial apoptosis by inducing annexin A5 expression and translocation in human prostate cancer cells, J. Toxicol. Environ. Health A, 77, 1467, 10.1080/15287394.2014.955834 You, 2014, PX-12 inhibits the growth of A549 lung cancer cells via G2/M phase arrest and ROS-dependent apoptosis, Int. J. Oncol., 44, 301, 10.3892/ijo.2013.2152 Wang, 2015, Thioredoxin-1 inhibitor, 1-methylpropyl 2-imidazolyl disulfide, inhibits the growth, migration and invasion of colorectal cancer cell lines, Oncol. Rep., 33, 967, 10.3892/or.2014.3652 Tan, 2014, Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxide, Int. J. Clin. Exp. Pathol., 7, 4765 Penning, 2007, Human aldo–keto reductases: function, gene regulation, and single nucleotide polymorphisms, Arch. Biochem. Biophys., 464, 241, 10.1016/j.abb.2007.04.024 Jin, 2005, Role of aldo–keto reductases in development of prostate and breast cancer, Front. Biosci.: J. Virtual Libr., 11, 2767, 10.2741/2006 Tai, 2007, Overexpression of aldo–keto reductase 1C2 as a high-risk factor in bladder cancer, Oncol. Rep., 17, 305 Laffin, 2012, Expression of the aldo–keto reductases AKR1B1 and AKR1B10 in human cancers, Front. Pharmacol., 3, 104, 10.3389/fphar.2012.00104 Yan, 2007, Aldo–keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: implication for cancer intervention, Int. J. Cancer, 121, 2301, 10.1002/ijc.22933 Penning, 2000, Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo–keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones, Biochem. J., 351, 67, 10.1042/bj3510067 Deng, 2002, Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells, J. Biol. Chem., 277, 15035, 10.1074/jbc.M112028200 Ueda, 2006, Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer, Gynecol. Oncol., 102, 173, 10.1016/j.ygyno.2005.12.009 Matsunaga, 2013, Pathophysiological roles of aldo–keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers, Chem. Biol. Interact., 202, 234, 10.1016/j.cbi.2012.09.024 Cui, 2009, Proteomic analysis of pancreatic ductal adenocarcinoma compared with normal adjacent pancreatic tissue and pancreatic benign cystadenoma, Pancreatology, 9, 89, 10.1159/000178879 Alzeer, 2011, The role of aldehyde reductase AKR1A1 in the metabolism of gamma-hydroxybutyrate in 1321N1 human astrocytoma cells, Chem. Biol. Interact., 191, 303, 10.1016/j.cbi.2011.01.018 Liu, 2009, Aldo–keto reductase family 1 member B1 inhibitors: old drugs with new perspectives, Recent Pat. Anti-cancer Drug Discov., 4, 246, 10.2174/157489209789206931 Chung, 2012, Overexpression and oncogenic function of aldo–keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma, Mod. Pathol., 25, 758, 10.1038/modpathol.2011.191 Bai, 2016, Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters, Drug Metab. Rev., 48, 541, 10.1080/03602532.2016.1197239 Selga, 2008, Transcriptional regulation of aldo–keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis, Biochem. Pharmacol., 75, 414, 10.1016/j.bcp.2007.08.034 Matsunaga, 2011, Involvement of the aldo–keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms, Anticancer Drugs, 22, 402, 10.1097/CAD.0b013e3283448df0 Huang, 2010, Overexpression of aldo–keto reductase 1C2 is associated with disease progression in patients with prostatic cancer, Histopathology, 57, 384, 10.1111/j.1365-2559.2010.03647.x Margis, 2008, Glutathione peroxidase family – an evolutionary overview, FEBS J., 275, 3959, 10.1111/j.1742-4658.2008.06542.x Chu, 2004, Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes, Cancer Res., 64, 962, 10.1158/0008-5472.CAN-03-2272 Walshe, 2007, Inactivation of glutathione peroxidase activity contributes to UV-induced squamous cell carcinoma formation, Cancer Res., 67, 4751, 10.1158/0008-5472.CAN-06-4192 Banning, 2011, Glutathione peroxidase 2 and its role in cancer, 271 Florian, 2001, Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue, Free Radic. Res., 35, 655, 10.1080/10715760100301181 Mork, 2000, Inverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP in colorectal adenomas compared with adjacent normal mucosa, Nutr. Cancer, 37, 108, 10.1207/S15327914NC3701_14 Mörk, 2003, Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus, Int. J. Cancer, 105, 300, 10.1002/ijc.11087 Banning, 2005, The GI-GPx gene is a target for Nrf2, Mol. Cell. Biol., 25, 4914, 10.1128/MCB.25.12.4914-4923.2005 Noh, 2000, Overexpression of peroxiredoxin in human breast cancer, Anticancer Res., 21, 2085 Chang, 2001, Augmented expression of peroxiredoxin I in lung cancer, Biochem. Biophys. Res. Commun., 289, 507, 10.1006/bbrc.2001.5989 Yanagawa, 1999, Peroxiredoxin I expression in human thyroid tumors, Cancer Lett., 145, 127, 10.1016/S0304-3835(99)00243-8 Yanagawa, 2000, Peroxiredoxin I expression in oral cancer: a potential new tumor marker, Cancer Lett., 156, 27, 10.1016/S0304-3835(00)00434-1 Kim, 2007, Elevated peroxiredoxin 1, but not NF-E2-related factor 2, is an independent prognostic factor for disease recurrence and reduced survival in stage I non-small cell lung cancer, Clin. Cancer Res., 13, 3875, 10.1158/1078-0432.CCR-06-2893 Chen, 2006, Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression, Int. J. Radiat. Oncol. Biol. Phys., 64, 581, 10.1016/j.ijrobp.2005.10.012 Sies, 1999, Glutathione and its role in cellular functions, Free Radic. Biol. Med., 27, 916, 10.1016/S0891-5849(99)00177-X Tatebe, 2002, Expression of heavy subunit of γ-glutamylcysteine synthetase (γ-GCSh) in human colorectal carcinoma, Int. J. Cancer, 97, 21, 10.1002/ijc.1574 Soini, 2001, Expression of γ-glutamyl cysteine synthetase in nonsmall cell lung carcinoma, Cancer, 92, 2911, 10.1002/1097-0142(20011201)92:11<2911::AID-CNCR10105>3.0.CO;2-G Seven, 1998, Breast cancer and benign breast disease patients evaluated in relation to oxidative stress, Cancer Biochem. Biophys., 16, 333 Carretero, 1999, Growth-associated changes in glutathione content correlate with liver metastatic activity of B16 melanoma cells, Clin. Exp. Metastasis, 17, 567, 10.1023/A:1006725226078 Calvert, 1998, Clinical studies of reversal of drug resistance based on glutathione, Chem. Biol. Interact., 111, 213, 10.1016/S0009-2797(98)00008-8 Iida, 1999, Co-expression of gamma-glutamylcysteine synthetase sub-units in response to cisplatin and doxorubicin in human cancer cells, Int. J. Cancer, 82, 405, 10.1002/(SICI)1097-0215(19990730)82:3<405::AID-IJC14>3.0.CO;2-M Kaur, 2008, Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinoma, Dis. Esophagus, 21, 103, 10.1111/j.1442-2050.2007.00742.x Fujimori, 2004, The subunits of glutamate cysteine ligase enhance cisplatin resistance in human non-small cell lung cancer xenografts in vivo, Int. J. Oncol., 25, 413 Meister, 1991, Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy, Pharmacol. Ther., 51, 155, 10.1016/0163-7258(91)90076-X O’Dwyer, 1996, Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer, J. Clin. Oncol., 14, 249, 10.1200/JCO.1996.14.1.249 Anderson, 1999, Depletion of glutathione by buthionine sulfoximine is cytotoxic for human neuroblastoma cell lines via apoptosis, Exp. Cell Res., 246, 183, 10.1006/excr.1998.4303 Ross, 2004, Quinone reductases multitasking in the metabolic world, Drug Metab. Rev., 36, 639, 10.1081/DMR-200033465 Siegel, 2004, NAD (P) H: quinone oxidoreductase 1: role as a superoxide scavenger, Mol. Pharmacol., 65, 1238, 10.1124/mol.65.5.1238 Cuendet, 2006, Quinone reductase induction as a biomarker for cancer chemoprevention, J. Nat. Prod., 69, 460, 10.1021/np050362q Long, 2000, NAD (P) H: quinone oxidoreductase 1 deficiency increases susceptibility to benzo (a) pyrene-induced mouse skin carcinogenesis, Cancer Res., 60, 5913 Schlager, 1990, (P) H:(Quinone-acceptor) oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol, Int. J. Cancer, 45, 403, 10.1002/ijc.2910450304 Mikami, 1998, Immunological quantitation of DT-diaphorase in carcinoma cell lines and clinical colon cancers: advanced tumors express greater levels of DT-diaphorase, Cancer Sci., 89, 910 Matsui, 2010, Dicoumarol enhances doxorubicin-induced cytotoxicity in p53 wild-type urothelial cancer cells through p38 activation, BJU Int., 105, 558, 10.1111/j.1464-410X.2009.08732.x Zeekpudsa, 2014, Suppression of NAD (P) H-quinone oxidoreductase 1 enhanced the susceptibility of cholangiocarcinoma cells to chemotherapeutic agents, J. Exp. Clin. Cancer Res., 33, 11, 10.1186/1756-9966-33-11 Bock, 2010, Functions and transcriptional regulation of adult human hepatic UDP-glucuronosyl-transferases (UGTs): mechanisms responsible for interindividual variation of UGT levels, Biochem. Pharmacol., 80, 771, 10.1016/j.bcp.2010.04.034 Kiang, 2005, UDP-glucuronosyltransferases and clinical drug–drug interactions, Pharmacol. Ther., 106, 97, 10.1016/j.pharmthera.2004.10.013 Saracino, 2007, Phytochemical regulation of UDP-glucuronosyltransferases: implications for cancer prevention, Nutrition and cancer, 59, 121, 10.1080/01635580701458178 Cummings, 2004, Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins, Biochem. Pharmacol., 67, 31, 10.1016/j.bcp.2003.07.019 Zahreddine, 2015, Molecular pathways: GLI1-induced drug glucuronidation in resistant cancer cells, Clin. Cancer Res., 21, 2207, 10.1158/1078-0432.CCR-14-1370 Li, 2014, Clinical significance of UGT1A1 gene polymorphisms on irinotecan-based regimens as the treatment in metastatic colorectal cancer, OncoTargets Ther., 7, 1653 Romero-Lorca, 2015, Impacts of the glucuronidase genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on tamoxifen metabolism in breast cancer patients, PLOS ONE, 10, e0132269, 10.1371/journal.pone.0132269 Hayes, 2005, Glutathione transferases, Annu. Rev. Pharmacol. Toxicol., 45, 51, 10.1146/annurev.pharmtox.45.120403.095857 Hayes, 1995, The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance part II, Crit. Rev. Biochem. Mol. Biol., 30, 521, 10.3109/10409239509083492 Perera, 2002, Associations between carcinogen–DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians’ Health Cohort Study, Carcinogenesis, 23, 1641, 10.1093/carcin/23.10.1641 Morari, 2002, The null genotype of glutathione s-transferase M1 and T1 locus increases the risk for thyroid cancer, Cancer Epidemiol. Prevent. Biomark., 11, 1485 Kote-Jarai, 2001, Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer, Pharmacogenet. Genomics, 11, 325, 10.1097/00008571-200106000-00007 Aktas, 2001, Glutathione S-transferase M1 gene polymorphism in bladder cancer patients: a marker for invasive bladder cancer?, Cancer Genet. Cytogenet., 125, 1, 10.1016/S0165-4608(00)00307-1 McLellan, 1999, Glutathione and glutathione-dependent enzymes in cancer drug resistance, Drug Resist. Updat., 2, 153, 10.1054/drup.1999.0083 Schisselbauer, 1990, Characterization of glutathione S-transferase expression in lymphocytes from chronic lymphocytic leukemia patients, Cancer Res., 50, 3562 Noda, 2011, Predictive value of expression of ERCC 1 and GST-p for 5-fluorouracil/oxaliplatin chemotherapy in advanced colorectal cancer, Hepato-gastroenterology, 59, 130 Ban, 1996, Transfection of glutathione S-transferase (GST)-π antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide, Cancer Res., 56, 3577 Johansson, 2006, Microsomal glutathione transferase 1 in anticancer drug resistance, Carcinogenesis, 28, 465, 10.1093/carcin/bgl148 Xu, 2014, Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway, Biochem. Pharmacol., 92, 220, 10.1016/j.bcp.2014.09.008 Young, 2001, Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer, Clin. Cancer Res., 7, 1798 Ma, 2014, Emodin augments cisplatin cytotoxicity in platinum-resistant ovarian cancer cells via ROS-dependent MRP1 downregulation, BioMed Res. Int., 2014, 10.1155/2014/107671 Zaman, 1995, Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein, Proc. Natl. Acad. Sci. U. S. A., 92, 7690, 10.1073/pnas.92.17.7690 Shim, 2009, Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway, Free Radic. Biol. Med., 47, 1619, 10.1016/j.freeradbiomed.2009.09.006 Paumi, 2001, Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity, J. Biol. Chem., 276, 7952, 10.1074/jbc.M009400200 Smitherman, 2004, Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity, J. Pharmacol. Exp. Ther., 308, 260, 10.1124/jpet.103.057729 Lin, 2014, Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway, Drug Des. Dev. Ther., 8, 973, 10.2147/DDDT.S65410 Das, 2015, Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of NRF2 signalling and modulation of inflammation in prevention of cancer, PLOS ONE, 10, e0124000, 10.1371/journal.pone.0124000 Tsai, 2011, Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation, Free Radic. Biol. Med., 51, 744, 10.1016/j.freeradbiomed.2011.05.016 Balstad, 2011, Coffee, broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo – studies in electrophile response element transgenic mice, Mol. Nut. Food Res., 55, 185, 10.1002/mnfr.201000204 Gao, 2013, Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway, Carcinogenesis, 34, 1806, 10.1093/carcin/bgt108