Oxidative versus Reductive Stress in Breast Cancer Development and Cellular Mechanism of Alleviation: A Current Perspective with Anti-breast Cancer Drug Resistance

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Abstract

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.

[1]
Kehrer JP, Lund LG. Cellular reducing equivalents and oxidative stress. Free Radic Biol Med 1994; 17(1): 65-75.
[http://dx.doi.org/10.1016/0891-5849(94)90008-6] [PMID: 7959167]
[2]
Studer L, Csete M, Lee SH, et al. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 2000; 20(19): 7377-83.
[http://dx.doi.org/10.1523/JNEUROSCI.20-19-07377.2000] [PMID: 11007896]
[3]
Ezashi T, Das P, Roberts RM. Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci 2005; 102(13): 4783-8.
[http://dx.doi.org/10.1073/pnas.0501283102] [PMID: 15772165]
[4]
Donato V, Bonora M, Simoneschi D, et al. The TDH–GCN5L1–Fbxo15–KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells. Nat Cell Biol 2017; 19(4): 341-51.
[http://dx.doi.org/10.1038/ncb3491] [PMID: 28319092]
[5]
Suzuki T, Yamamoto M. Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress. J Biol Chem 2017; 292(41): 16817-24.
[http://dx.doi.org/10.1074/jbc.R117.800169] [PMID: 28842501]
[6]
Buckley SM, Aranda-Orgilles B, Strikoudis A, et al. Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell 2012; 11(6): 783-98.
[http://dx.doi.org/10.1016/j.stem.2012.09.011] [PMID: 23103054]
[7]
Balchin D, Hayer-Hartl M, Hartl FU. In vivo aspects of protein folding and quality control. Science 2016; 353(6294): aac4354.
[http://dx.doi.org/10.1126/science.aac4354] [PMID: 27365453]
[8]
Rape M. Ubiquitylation at the crossroads of development and disease. Nat Rev Mol Cell Biol 2018; 19(1): 59-70.
[http://dx.doi.org/10.1038/nrm.2017.83] [PMID: 28928488]
[9]
Oh E, Akopian D, Rape M. Principles of ubiquitin-dependent signaling. Annu Rev Cell Dev Biol 2018; 34(1): 137-62.
[http://dx.doi.org/10.1146/annurev-cellbio-100617-062802] [PMID: 30110556]
[10]
Yau R, Rape M. The increasing complexity of the ubiquitin code. Nat Cell Biol 2016; 18(6): 579-86.
[http://dx.doi.org/10.1038/ncb3358] [PMID: 27230526]
[11]
Wakabayashi N, Itoh K, Wakabayashi J, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet 2003; 35(3): 238-45.
[http://dx.doi.org/10.1038/ng1248] [PMID: 14517554]
[12]
Itoh K, Wakabayashi N, Katoh Y, Ishii T, O’Connor T, Yamamoto M. Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 2003; 8(4): 379-91.
[http://dx.doi.org/10.1046/j.1365-2443.2003.00640.x] [PMID: 12653965]
[13]
Zhang DD, Lo SC, Cross JV, Templeton DJ, Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 2004; 24(24): 10941-53.
[http://dx.doi.org/10.1128/MCB.24.24.10941-10953.2004] [PMID: 15572695]
[14]
Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol 2005; 25(1): 162-71.
[http://dx.doi.org/10.1128/MCB.25.1.162-171.2005] [PMID: 15601839]
[15]
Kaelin WG Jr. Von hippel-lindau disease. Annu Rev Pathol 2007; 2(1): 145-73.
[http://dx.doi.org/10.1146/annurev.pathol.2.010506.092049] [PMID: 18039096]
[16]
Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 2008; 8(9): 705-13.
[http://dx.doi.org/10.1038/nrc2468] [PMID: 19143055]
[17]
Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: A diabolic liaison. Int J Cell Biol 2012; 2012: 1-8.
[http://dx.doi.org/10.1155/2012/762825] [PMID: 22666258]
[18]
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010; 49(11): 1603-16.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[19]
Zhou D, Shao L, Spitz DR. Reactive oxygen species in normal and tumor stem cells. Adv Cancer Res 2014; 122: 1-67.
[http://dx.doi.org/10.1016/B978-0-12-420117-0.00001-3] [PMID: 24974178]
[20]
Loft S, Olsen A, Møller P, Poulsen HE, Tjønneland A. Association between 8-oxo-7,8-dihydro-2′-deoxyguanosine excretion and risk of postmenopausal breast cancer: Nested case-control study. Cancer Epidemiol Biomarkers Prev 2013; 22(7): 1289-96.
[http://dx.doi.org/10.1158/1055-9965.EPI-13-0229] [PMID: 23658396]
[21]
Yang S, Pinney SM, Mallick P, Ho SM, Bracken B, Wu T. Impact of oxidative stress biomarkers and carboxymethyllysine (an advanced glycation end product) on prostate cancer: A prospective study. Clin Genitourin Cancer 2015; 13(5): e347-51.
[http://dx.doi.org/10.1016/j.clgc.2015.04.004] [PMID: 25972296]
[22]
Pennington JD, Wang TJC, Nguyen P, et al. Redox-sensitive signaling factors as a novel molecular targets for cancer therapy. Drug Resist Updat 2005; 8(5): 322-30.
[http://dx.doi.org/10.1016/j.drup.2005.09.002] [PMID: 16230045]
[23]
Eliyatkin N, Yalçın E, Zengel B, Aktaş S, Vardar E. Molecular classification of breast carcinoma: from traditional, old-fashioned way to a new age, and a new way. J Breast Health 2015; 11(2): 59-66.
[http://dx.doi.org/10.5152/tjbh.2015.1669] [PMID: 28331693]
[24]
Joensuu K, Leidenius M, Kero M, Andersson LC, Horwitz KB, Heikkilä P. ER, PR, HER2, Ki-67 and CK5 in early and late relapsing breast cancer—reduced ck5 expression in metastases. Breast Cancer 2013; 7: BCBCR.S10701.
[http://dx.doi.org/10.4137/BCBCR.S10701] [PMID: 23514931]
[25]
Tascioglu Aliyev A, Panieri E, Stepanić V, Gurer-Orhan H, Saso L. Involvement of NRF2 in breast cancer and possible therapeutical role of polyphenols and melatonin. Molecules 2021; 26(7): 1853.
[http://dx.doi.org/10.3390/molecules26071853] [PMID: 33805996]
[26]
Chun KS, Kim DH, Surh YJ. Role of reductive versus oxidative stress in tumor progression and anticancer drug resistance. Cells 2021; 10(4): 758.
[http://dx.doi.org/10.3390/cells10040758] [PMID: 33808242]
[27]
Ray SK, Mukherjee S. Cancer stem cells: Current status and therapeutic implications in cancer therapy-a new paradigm. Curr Stem Cell Res Ther 2021; 16(8): 970-9.
[http://dx.doi.org/10.2174/1574888X16666210203105800] [PMID: 33563175]
[28]
Yao S, Fan LYN, Lam EWF. The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance. Semin Cancer Biol 2018; 50: 77-89.
[http://dx.doi.org/10.1016/j.semcancer.2017.11.018] [PMID: 29180117]
[29]
Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016; 2016: 1-44.
[http://dx.doi.org/10.1155/2016/1245049] [PMID: 27478531]
[30]
Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxid Redox Signal 2018; 28(3): 251-72.
[http://dx.doi.org/10.1089/ars.2017.7216] [PMID: 28648096]
[31]
Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010; 44(5): 479-96.
[http://dx.doi.org/10.3109/10715761003667554] [PMID: 20370557]
[32]
Gào X, Schöttker B. Reduction-oxidation pathways involved in cancer development: A systematic review of literature reviews. Oncotarget 2017; 8(31): 51888-906.
[http://dx.doi.org/10.18632/oncotarget.17128] [PMID: 28881698]
[33]
Verschoor ML, Wilson LA, Singh G. Mechanisms associated with mitochondrial-generated reactive oxygen species in cancerthis article is one of a selection of papers published in a special issue on oxidative stress in health and disease. Can J Physiol Pharmacol 2010; 88(3): 204-19.
[http://dx.doi.org/10.1139/Y09-135] [PMID: 20393586]
[34]
Holmström KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 2014; 15(6): 411-21.
[http://dx.doi.org/10.1038/nrm3801] [PMID: 24854789]
[35]
Wallace DC. Mitochondria and cancer. Nat Rev Cancer 2012; 12(10): 685-98.
[http://dx.doi.org/10.1038/nrc3365] [PMID: 23001348]
[36]
Tokarz P, Blasiak J. Role of mitochondria in carcinogenesis. Acta Biochim Pol 2014; 61(4): 671-8.
[http://dx.doi.org/10.18388/abp.2014_1829] [PMID: 25493442]
[37]
Landry WD, Cotter TG. ROS signalling, NADPH oxidases and cancer. Biochem Soc Trans 2014; 42(4): 934-8.
[http://dx.doi.org/10.1042/BST20140060] [PMID: 25109982]
[38]
Meitzler JL, Antony S, Wu Y, et al. NADPH oxidases: A perspective on reactive oxygen species production in tumor biology. Antioxid Redox Signal 2014; 20(17): 2873-89.
[http://dx.doi.org/10.1089/ars.2013.5603] [PMID: 24156355]
[39]
Speed N, Blair IA. Cyclooxygenase- and lipoxygenase-mediated DNA damage. Cancer Metastasis Rev 2011; 30(3-4): 437-47.
[http://dx.doi.org/10.1007/s10555-011-9298-8] [PMID: 22009064]
[40]
Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol 2013; 64(4): 409-21.
[PMID: 24101387]
[41]
Knab LM, Grippo PJ, Bentrem DJ. Involvement of eicosanoids in the pathogenesis of pancreatic cancer: The roles of cyclooxygenase-2 and 5-lipoxygenase. World J Gastroenterol 2014; 20(31): 10729-39.
[http://dx.doi.org/10.3748/wjg.v20.i31.10729] [PMID: 25152576]
[42]
Vannini F, Kashfi K, Nath N. The dual role of iNOS in cancer. Redox Biol 2015; 6: 334-43.
[http://dx.doi.org/10.1016/j.redox.2015.08.009] [PMID: 26335399]
[43]
Bogdan C. Nitric oxide synthase in innate and adaptive immunity: An update. Trends Immunol 2015; 36(3): 161-78.
[http://dx.doi.org/10.1016/j.it.2015.01.003] [PMID: 25687683]
[44]
Sabharwal SS, Schumacker PT. Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles’ heel? Nat Rev Cancer 2014; 14(11): 709-21.
[http://dx.doi.org/10.1038/nrc3803] [PMID: 25342630]
[45]
Bae I, Fan S, Meng Q, et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res 2004; 64(21): 7893-909.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1119] [PMID: 15520196]
[46]
Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011; 19(3): 387-400.
[http://dx.doi.org/10.1016/j.ccr.2011.01.038] [PMID: 21397861]
[47]
DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011; 475(7354): 106-9.
[http://dx.doi.org/10.1038/nature10189] [PMID: 21734707]
[48]
Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: Involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 2005; 16(10): 577-86.
[http://dx.doi.org/10.1016/j.jnutbio.2005.05.013] [PMID: 16111877]
[49]
Liu Y, Li Q, Zhou L, et al. Cancer drug resistance: Redox resetting renders a way. Oncotarget 2106; 7(27): 42740-61.
[http://dx.doi.org/10.18632/oncotarget.8600] [PMID: 27057637]
[50]
Zabłocka A, Janusz M. Dwa oblicza wolnych rodników tlenowych. Postepy Hig Med Dosw 2008; 62: 118-24. [The two faces of reactive oxygen species].
[51]
Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013; 53(1): 401-26.
[http://dx.doi.org/10.1146/annurev-pharmtox-011112-140320] [PMID: 23294312]
[52]
Manford AG, Rodríguez-Pérez F, Shih KY, et al. A cellular mechanism to detect and alleviate reductive stress. Cell 2020; 183(1): 46-61.e21.
[http://dx.doi.org/10.1016/j.cell.2020.08.034] [PMID: 32941802]
[53]
Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 2016; 73(17): 3221-47.
[http://dx.doi.org/10.1007/s00018-016-2223-0] [PMID: 27100828]
[54]
Pall ML, Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao 2015; 67(1): 1-18.
[PMID: 25672622]
[55]
Dodson M, Redmann M, Rajasekaran NS, Darley-Usmar V, Zhang J. KEAP1–NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity. Biochem J 2015; 469(3): 347-55.
[http://dx.doi.org/10.1042/BJ20150568] [PMID: 26205490]
[56]
Augimeri G, Giordano C, Gelsomino L, et al. The role of PPARγ ligands in breast cancer: From basic research to clinical studies. Cancers 2020; 12(9): 2623.
[http://dx.doi.org/10.3390/cancers12092623] [PMID: 32937951]
[57]
Gorrini C, Gang BP, Bassi C, et al. Estrogen controls the survival of BRCA1-deficient cells viaa PI3K–NRF2-regulated pathway. Proc Natl Acad Sci 2014; 111(12): 4472-7.
[http://dx.doi.org/10.1073/pnas.1324136111] [PMID: 24567396]
[58]
Kim EK, Choi EJ. Compromised MAPK signaling in human diseases: An update. Arch Toxicol 2015; 89(6): 867-82.
[http://dx.doi.org/10.1007/s00204-015-1472-2] [PMID: 25690731]
[59]
Barthel A, Klotz LO. Phosphoinositide 3-kinase signaling in the cellular response to oxidative stress. Biol Chem 2005; 386(3): 207-16.
[http://dx.doi.org/10.1515/BC.2005.026] [PMID: 15843166]
[60]
Yang Q, Lee JD. Targeting the BMK1 MAP kinase pathway in cancer therapy. Clin Cancer Res 2011; 17(11): 3527-32.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2504] [PMID: 21385929]
[61]
Yousefi B, Samadi N, Ahmadi Y. Akt and p53R2, partners that dictate the progression and invasiveness of cancer. DNA Repair 2014; 22: 24-9.
[http://dx.doi.org/10.1016/j.dnarep.2014.07.001] [PMID: 25086499]
[62]
Gocek E, Moulas AN, Studzinski GP. Non-receptor protein tyrosine kinases signaling pathways in normal and cancer cells. Crit Rev Clin Lab Sci 2014; 51(3): 125-37.
[http://dx.doi.org/10.3109/10408363.2013.874403] [PMID: 24446827]
[63]
Chiarugi P. ReviewPTPs versus PTKs: The redox side of the coin. Free Radic Res 2005; 39(4): 353-64.
[http://dx.doi.org/10.1080/10715760400027987] [PMID: 16028361]
[64]
Tonks NK. Protein tyrosine phosphatases: From genes, to function, to disease. Nat Rev Mol Cell Biol 2006; 7(11): 833-46.
[http://dx.doi.org/10.1038/nrm2039] [PMID: 17057753]
[65]
Giorgi C, Agnoletto C, Baldini C, et al. Redox control of protein kinase C: Cell- and disease-specific aspects. Antioxid Redox Signal 2010; 13(7): 1051-85.
[http://dx.doi.org/10.1089/ars.2009.2825] [PMID: 20136499]
[66]
Garg R, Benedetti LG, Abera MB, Wang H, Abba M, Kazanietz MG. Protein kinase C and cancer: What we know and what we do not. Oncogene 2014; 33(45): 5225-37.
[http://dx.doi.org/10.1038/onc.2013.524] [PMID: 24336328]
[67]
Shelton P, Jaiswal AK. The transcription factor NF‐E2‐related Factor 2 (Nrf2): A protooncogene? FASEB J 2013; 27(2): 414-23.
[http://dx.doi.org/10.1096/fj.12-217257] [PMID: 23109674]
[68]
Na HK, Surh YJ. Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1. Free Radic Biol Med 2014; 67: 353-65.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.819] [PMID: 24200599]
[69]
Leinonen HM, Kansanen E, Pölönen P, Heinäniemi M, Levonen AL. Role of the Keap1-Nrf2 pathway in cancer. Adv Cancer Res 2014; 122: 281-320.
[http://dx.doi.org/10.1016/B978-0-12-420117-0.00008-6] [PMID: 24974185]
[70]
Xiang M, Namani A, Wu S, Wang X. Nrf2: Bane or blessing in cancer? J Cancer Res Clin Oncol 2014; 140(8): 1251-9.
[http://dx.doi.org/10.1007/s00432-014-1627-1] [PMID: 24599821]
[71]
Aggarwal B, Sethi G, Nair A, Ichikawa H. Nuclear factorkappa B: A holy grail in cancer prevention and therapy. Curr Signal Transduct Ther 2006; 1(1): 25-52.
[http://dx.doi.org/10.2174/157436206775269235]
[72]
Sarkar FH, Li Y, Wang Z, Kong D. NF-kappaB signaling pathway and its therapeutic implications in human diseases. Int Rev Immunol 2008; 27(5): 293-319.
[http://dx.doi.org/10.1080/08830180802276179] [PMID: 18853341]
[73]
Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 2009; 1(4): a000034.
[http://dx.doi.org/10.1101/cshperspect.a000034] [PMID: 20066092]
[74]
Zhao J, Du F, Shen G, Zheng F, Xu B. The role of hypoxia-inducible factor-2 in digestive system cancers. Cell Death Dis 2015; 6(1): e1600.
[http://dx.doi.org/10.1038/cddis.2014.565] [PMID: 25590810]
[75]
Movafagh S, Crook S, Vo K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: new developments in an old debate. J Cell Biochem 2015; 116(5): 696-703.
[http://dx.doi.org/10.1002/jcb.25074] [PMID: 25546605]
[76]
Eferl R, Wagner EF. AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer 2003; 3(11): 859-68.
[http://dx.doi.org/10.1038/nrc1209] [PMID: 14668816]
[77]
Ladelfa MF, Toledo MF, Laiseca JE, Monte M. Interaction of p53 with tumor suppressive and oncogenic signaling pathways to control cellular reactive oxygen species production. Antioxid Redox Signal 2011; 15(6): 1749-61.
[http://dx.doi.org/10.1089/ars.2010.3652] [PMID: 20919943]
[78]
Kotsinas A, Aggarwal V, Tan EJ, Levy B, Gorgoulis VG. PIG3: A novel link between oxidative stress and DNA damage response in cancer. Cancer Lett 2012; 327(1-2): 97-102.
[http://dx.doi.org/10.1016/j.canlet.2011.12.009] [PMID: 22178897]
[79]
Vurusaner B, Poli G, Basaga H. Tumor suppressor genes and ROS: Complex networks of interactions. Free Radic Biol Med 2012; 52(1): 7-18.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.035] [PMID: 22019631]
[80]
Storz P. Forkhead homeobox type O transcription factors in the responses to oxidative stress. Antioxid Redox Signal 2011; 14(4): 593-605.
[http://dx.doi.org/10.1089/ars.2010.3405] [PMID: 20618067]
[81]
Myatt SS, Brosens JJ, Lam EWF. Sense and sensitivity: FOXO and ROS in cancer development and treatment. Antioxid Redox Signal 2011; 14(4): 675-87.
[http://dx.doi.org/10.1089/ars.2010.3383] [PMID: 20649462]
[82]
Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat Rev Cancer 2009; 9(11): 798-809.
[http://dx.doi.org/10.1038/nrc2734] [PMID: 19851315]
[83]
Cuzziol CI, Castanhole-Nunes MMU, Pavarino ÉC, Goloni-Bertollo EM. MicroRNAs as regulators of VEGFA and NFE2L2 in cancer. Gene 2020; 759: 144994.
[http://dx.doi.org/10.1016/j.gene.2020.144994] [PMID: 32721475]
[84]
Singh A, Misra V, Thimmulappa RK, et al. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med 2006; 3(10): e420.
[http://dx.doi.org/10.1371/journal.pmed.0030420] [PMID: 17020408]
[85]
Solis L, Carmen B, Wenli D. Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinico-pathologic features. Clin Cancer Res 2010; 16(14): 3743-53.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3352]
[86]
Zhao XJ, Yu HW, Yang YZ, et al. Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol 2018; 18: 124-37.
[http://dx.doi.org/10.1016/j.redox.2018.07.002] [PMID: 30014902]
[87]
Li Z, Xu L, Tang N, et al. The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing the transcription factor Nrf2. FEBS Lett 2014; 588(17): 3000-7.
[http://dx.doi.org/10.1016/j.febslet.2014.05.057] [PMID: 24928441]
[88]
Muscarella LA, Parrella P, D’Alessandro V, et al. Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer. Epigenetics 2011; 6(6): 710-9.
[http://dx.doi.org/10.4161/epi.6.6.15773] [PMID: 21610322]
[89]
Zhang S, Duan S, Xie Z, et al. Epigenetic therapeutics targeting nrf2/keap1 signaling in cancer oxidative stress. Front Pharmacol 2022; 13: 924817.
[http://dx.doi.org/10.3389/fphar.2022.924817] [PMID: 35754474]
[90]
Tell G, Quadrifoglio F, Tiribelli C, Kelley MR. The many functions of APE1/Ref-1: Not only a DNA repair enzyme. Antioxid Redox Signal 2009; 11(3): 601-19.
[http://dx.doi.org/10.1089/ars.2008.2194] [PMID: 18976116]
[91]
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis. JAMA 2007; 297(8): 842-57.
[http://dx.doi.org/10.1001/jama.297.8.842] [PMID: 17327526]
[92]
Turpaev KT. Keap1-Nrf2 signaling pathway: Mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles. Biochemistry 2013; 78(2): 111-26.
[http://dx.doi.org/10.1134/S0006297913020016] [PMID: 23581983]
[93]
Baird L, Yamamoto M. The molecular mechanisms regulating the keap1-nrf2 pathway. Mol Cell Biol 2020; 40(13): e00099-20.
[http://dx.doi.org/10.1128/MCB.00099-20] [PMID: 32284348]
[94]
Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 2011; 16(2): 123-40.
[http://dx.doi.org/10.1111/j.1365-2443.2010.01473.x] [PMID: 21251164]
[95]
Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Cancer Cell 2018; 34(1): 21-43.
[http://dx.doi.org/10.1016/j.ccell.2018.03.022] [PMID: 29731393]
[96]
Heo JM, Ordureau A, Swarup S, et al. RAB7A phosphorylation by TBK1 promotes mitophagy viathe PINK-PARKIN pathway. Sci Adv 2018; 4(11): eaav0443.
[http://dx.doi.org/10.1126/sciadv.aav0443] [PMID: 30627666]
[97]
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: An evolving paradigm. Nat Rev Cancer 2013; 13(10): 714-26.
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863]
[98]
Fojo T, Bates S. Strategies for reversing drug resistance. Oncogene 2003; 22(47): 7512-23.
[http://dx.doi.org/10.1038/sj.onc.1206951] [PMID: 14576855]
[99]
Meister A. Glutathione deficiency produced by inhibition of its synthesis, and its reversal; Applications in research and therapy. Pharmacol Ther 1991; 51(2): 155-94.
[http://dx.doi.org/10.1016/0163-7258(91)90076-X] [PMID: 1784629]
[100]
Ortega AL, Mena S, Estrela JM. Glutathione in cancer cell death. Cancers 2011; 3(1): 1285-310.
[http://dx.doi.org/10.3390/cancers3011285] [PMID: 24212662]
[101]
Hart PC, Mao M, de Abreu ALP, et al. MnSOD upregulation sustains the Warburg effect viamitochondrial ROS and AMPK-dependent signalling in cancer. Nat Commun 2015; 6(1): 6053.
[http://dx.doi.org/10.1038/ncomms7053] [PMID: 25651975]
[102]
Townsend DM, Tew KD. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 2003; 22(47): 7369-75.
[http://dx.doi.org/10.1038/sj.onc.1206940] [PMID: 14576844]
[103]
Saleh EM, El-Awady RA, Abdel Alim MA, Abdel Wahab AHA. Altered expression of proliferation-inducing and proliferation-inhibiting genes might contribute to acquired doxorubicin resistance in breast cancer cells. Cell Biochem Biophys 2009; 55(2): 95-105.
[http://dx.doi.org/10.1007/s12013-009-9058-3] [PMID: 19593673]
[104]
Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev 2017; 2017: 1-13.
[http://dx.doi.org/10.1155/2017/8416763] [PMID: 28819546]
[105]
Wondrak GT. Redox-directed cancer therapeutics: Molecular mechanisms and opportunities. Antioxid Redox Signal 2009; 11(12): 3013-69.
[http://dx.doi.org/10.1089/ars.2009.2541] [PMID: 19496700]