Cellular systems responsible for the formation and removal of reactive oxygen species (ROS), functioning within physiological limits, are essential for maintaining intracellular redox balance. This state is known as oxidative eustress. Key redox signaling molecules, such as superoxide anion radical (O2•-) and hydrogen peroxide (H2O2), operate at nanomolar concentrations and are produced by NADPH oxidases (regulated by various factors), the mitochondrial electron transport chain (ETC), and numerous enzymes. In addition, cell signaling is influenced by nitric oxide (NO•) and reactive lipid species. Disruption of ROS signaling can lead to oxidative stress, a harmful condition associated with many chronic diseases, including cancer. The dual nature of ROS is evident in premalignant and malignant cells at all stages of tumor development, including proliferation, migration/invasion, angiogenesis, inflammation, immune evasion, and metastasis. ROS can promote tumor formation by regulating immune cells, mitochondrial metabolism, DNA methylation, DNA damage [such as the DNA oxidation product, 8-oxo-dG, resulting from hydroxyl radical (•OH) attack], and other mechanisms. The tumor-promoting activity mediated by H2O2 manifests through the promotion of epithelial-to-mesenchymal transition (EMT) and the formation of the tumor microenvironment (TME) by tumor-associated macrophages. While ROS are vital for tumor initiation and growth, their excessive production can also have anticancer effects by inducing senescence, apoptosis, or necrosis. ROS-related anticancer mechanisms include mitochondrial dysfunction, p53-dependent apoptosis, iron-dependent ferroptosis, activation of endoplasmic reticulum stress, inhibition of growth signaling pathways (such as the epidermal growth factor pathway, EGF), among others. Tumor cells employ a range of adaptive mechanisms to effectively maintain ROS levels within a dynamic range that promotes proliferation while preventing cell death. This regulation is achieved by fine-tuning the effects of antioxidants throughout all stages of cancer. During early tumor development, characterized by increased oncogene-induced oxidative stress, cancer cells depend on glutathione (GSH) and upregulated antioxidant gene expression controlled by nuclear factor erythroid 2-related factor 2 (NRF2) to maintain redox balance. The opposing roles of certain antioxidant enzymes, such as Mn-SOD (SOD2), illustrate the same duality as ROS, acting as potential tumor suppressors during early carcinogenesis and as tumor promoters during metastasis. Low-molecular-weight antioxidants such as vitamins C (ascorbate) and E (tocopherols), carotenoids (e.g., lycopene, β-carotene), flavonoids (e.g., quercetin), and isoflavones demonstrate effective antioxidant activity in vitro, but their anticancer effects in clinical settings remain unproven. Understanding the influence of the antioxidant network and the redox threshold on epithelial-to-mesenchymal transition and key tumor microenvironment components could lead to more effective therapeutic strategies. This review explores the dual roles of ROS and antioxidants throughout different stages of cancer progression.

Biomedical Research Center University Hospital Hradec Kralove 5005 Hradec Kralove Czech Republic

Center of Advanced Innovation Technologies VSB Technical University of Ostrava 708 00 Ostrava Poruba Czech Republic

Centre for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Department of Chemistry Faculty of Natural Sciences Constantine the Philosopher University in Nitra 949 74 Nitra Slovakia

Department of Chemistry Faculty of Sciences University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Doping Research Chair Zoology Department College of Science King Saud University 11451 Riyadh Saudi Arabia

Faculty of Chemical and Food Technology Slovak University of Technology 812 37 Bratislava Slovakia

Zobrazit více v PubMed

Abate C, Curran T (1990) Encounters with fos and jun on the road to AP-1. Semin Cancer Biol 1(1):19–26 PubMed

ATBC Trial Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330(15):1029–1035. https://doi.org/10.1056/NEJM199404143301501 DOI

Adamska A, Stefanowicz-Hajduk J, Ochocka JR (2019) Alpha-hederin, the active saponin of Nigella sativa, as an anticancer agent inducing apoptosis in the SKOV-3 cell line. Molecules 24(16):2958. https://doi.org/10.3390/molecules24162958 PubMed DOI PMC

Afanasev I (2013) New nucleophilic mechanisms of ROS-dependent epigenetic modifications: comparison of aging and cancer. Aging Dis 5(1):52–62. https://doi.org/10.14336/AD.2014.050052 PubMed DOI

Aggarwal V, Tuli HS, Varol A, Thakral F (2019) Role of reactive oxygen species in cancer progression: molecular mechanisms and recent advancements. Biomolecules 9(11):735. https://doi.org/10.3390/biom9110735 PubMed DOI PMC

Ahmad Bhat I, Maqsood Bhat A, Tasduq Abdullah S (2025) Apoptosis-mechanisms, regulation in pathology, and therapeutic potential. Cell death regulation in pathology. IntechOpen. https://doi.org/10.5772/intechopen.1008890 DOI

An X, Yu W, Liu J et al (2024) Oxidative cell death in cancer: mechanisms and therapeutic opportunities. Cell Death Dis 15:556. https://doi.org/10.1038/s41419-024-06939-5 PubMed DOI PMC

Anastasiou D, Poulogiannis G, Asara JM, Boxer MB et al (2011) Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334(6060):1278–1283. https://doi.org/10.1126/science.1211485 PubMed DOI PMC

Arnandis T, Monteiro P, Adams SD et al (2018) Oxidative stress in cells with extra centrosomes drives non-cell-autonomous invasion. Dev Cell 47(4):409-424.e9. https://doi.org/10.1016/j.devcel.2018.10.026 PubMed DOI PMC

Arsova-Sarafinovska Z, Matevska N, Eken A, Petrovski D et al (2009) Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int Urol Nephrol 41:63–70. https://doi.org/10.1007/s11255-008-9407-y PubMed DOI

Aubrey B, Kelly G, Janic A et al (2018) How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ 25:104–113. https://doi.org/10.1038/cdd.2017.169 PubMed DOI

Aune D, Chan DS, Vieira AR, Navarro Rosenblatt DA et al (2012) Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 96(2):356–373. https://doi.org/10.3945/ajcn.112.034165 PubMed DOI

Azzi A (2022) Oxidative stress: what is it? can it be measured? where is it located? can it be good or bad? can it be prevented? can it be cured? Antioxidants (Basel) 11(8):1431. https://doi.org/10.3390/antiox11081431 PubMed DOI

Badawi Y, Ramamoorthy P, Shi H (2012) Hypoxia-inducible factor 1 protects hypoxic astrocytes against glutamate toxicity. ASN Neuro 4(4):231–241. https://doi.org/10.1042/AN20120006 PubMed DOI

Bai Y, Han T, Dong Y, Liang C et al (2024) GPX8 PubMed DOI PMC

Baker AM, Oberley LW, Cohen MB (1997) Expression of antioxidant enzymes in human prostatic adenocarcinoma. Prostate 32:229–233. https://doi.org/10.1002/(SICI)1097-0045(19970901)32:4%3c229::AID-PROS1%3e3.0.CO;2-E PubMed DOI

Bakhoum SF, Ngo B, Laughney AM et al (2018) Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553(7689):467–472. https://doi.org/10.1038/nature25432 PubMed DOI PMC

Bănescu C, Trifa AP, Voidăzan S, Moldovan VG et al (2014) CAT, GPX1, MnSOD, GSTM1, GSTT1, and GSTP1 genetic polymorphisms in chronic myeloid leukemia: a case-control study. Oxid Med Cell Longev 2014:875861. https://doi.org/10.1155/2014/875861 PubMed DOI PMC

Barna J, Csermely P, Vellai T (2018) Roles of heat shock factor 1 beyond the heat shock response. Cell Mol Life Sci 75(16):2897–2916. https://doi.org/10.1007/s00018-018-2836-6 PubMed DOI PMC

Barondeau DP, Kassmann CJ, Bruns CK, Tainer JA, Getzoff ED (2004) Nickel superoxide dismutase structure and mechanism. Biochemistry 43(25):8038–8047. https://doi.org/10.1021/bi0496081 PubMed DOI

Barrett CW, Ning W, Chen X et al (2013) Tumor suppressor function of the plasma glutathione peroxidase gpx3 in colitis-associated carcinoma. Cancer Res 73(3):1245–1255. https://doi.org/10.1158/0008-5472.CAN-12-3150 PubMed DOI

Bartek J (2011) DNA damage response, genetic instability and cancer: from mechanistic insights to personalized treatment. Mol Oncol 5(4):303–307. https://doi.org/10.1016/j.molonc.2011.07.006 PubMed DOI PMC

Basak D, Punganuru SR, Srivenugopal KS (2016) Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor. Int J Oncol 48(4):1426–1436. https://doi.org/10.3892/ijo.2016.3372 PubMed DOI

Bause AS, Haigis MC (2013) SIRT3 regulation of mitochondrial oxidative stress. Exp Gerontol 48(7):634–639. https://doi.org/10.1016/j.exger.2012.08.007 PubMed DOI

Benhar M (2018) Roles of mammalian glutathione peroxidase and thioredoxin reductase enzymes in the cellular response to nitrosative stress. Free Radic Biol Med 127:160–164. https://doi.org/10.1016/j.freeradbiomed.2018.01.028 PubMed DOI

Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126(1):107–120. https://doi.org/10.1016/j.cell.2006.05.036 PubMed DOI

Bieging KT, Mello SS, Attardi LD (2014) Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 14(5):359–370. https://doi.org/10.1038/nrc3711 PubMed DOI PMC

Bizoń A, Chojdak-Łukasiewicz J, Budrewicz S, Pokryszko-Dragan A, Piwowar A (2023) Exploring the relationship between antioxidant enzymes, oxidative stress markers, and clinical profile in relapsing-remitting multiple sclerosis. Antioxidants 12(8):1638. https://doi.org/10.3390/antiox12081638 PubMed DOI PMC

Boroughs LK, DeBerardinis RJ (2015) Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 17(4):351–359. https://doi.org/10.1038/ncb3124 PubMed DOI PMC

Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134(3):707–716. https://doi.org/10.1042/bj1340707 PubMed DOI PMC

Brigelius-Flohé R, Kipp A (2009) Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta 1790(11):1555–1568. https://doi.org/10.1016/j.bbagen.2009.03.006 PubMed DOI

Brigelius-Flohé R, Maiorino M (2013) Glutathione peroxidases. Biochim Biophys Acta 1830(5):3289–3303. https://doi.org/10.1016/j.bbagen.2012.11.020 PubMed DOI

Brown AK, Webb AE (2018) Regulation of FOXO factors in mammalian cells. Curr Top Dev Biol 127:165–192. https://doi.org/10.1016/bs.ctdb.2017.10.006 PubMed DOI

Burrage EN, Coblentz T, Prabhu SS, Childers R et al (2023) Xanthine oxidase mediates chronic stress-induced cerebrovascular dysfunction and cognitive impairment. J Cereb Blood Flow Metab 43(6):905–920. https://doi.org/10.1177/0271678X231152551 PubMed DOI PMC

Busuttil RA, Garcia AM, Cabrera C et al (2005) Organ-specific increase in mutation accumulation and apoptosis rate in CuZn-superoxide dismutase-deficient mice. Cancer Res 65(24):11271–11275. https://doi.org/10.1158/0008-5472.CAN-05-2980 PubMed DOI

Caino MC, Ghosh JC, Chae YC et al (2015) PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion. Proc Natl Acad Sci U S A 112(28):863843. https://doi.org/10.1073/pnas.1500722112 DOI

Cavallini C, Chignola R, Dando I, Perbellini O et al (2018) Low catalase expression confers redox hypersensitivity and identifies an indolent clinical behavior in CLL. Blood 131(17):1942–1954. https://doi.org/10.1182/blood-2017-08-800466 PubMed DOI

Chang TP, Poltoratsky V, Vancurova I (2015) Bortezomib inhibits expression of TGF-β1, IL-10, and CXCR4, resulting in decreased survival and migration of cutaneous T cell lymphoma cells. J Immunol 194(6):2942–2953. https://doi.org/10.4049/jimmunol.1402610 PubMed DOI

Chen A, Huang H, Fang S, Hang Q (2024) ROS: a “booster” for chronic inflammation and tumor metastasis. Biochim Biophys Acta Rev Cancer 1879:189175. https://doi.org/10.1016/j.bbcan.2024.189175 DOI

Chen L, Zhang Z, Hoshino A, Zheng HD, Morley M, Arany Z, Rabinowitz JD (2019) NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism. Nat Metab 1:404–415. https://doi.org/10.1038/s42255-019-0043-x PubMed DOI PMC

Chen L, Min J, Wang F (2022) Copper homeostasis and cuproptosis in health and disease. Sig Transduct Target Ther 7:378. https://doi.org/10.1038/s41392-022-01229-y DOI

Chen Z, Han F, Du Y et al (2023) Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther 8:70. https://doi.org/10.1038/s41392-023-01332-8 PubMed DOI PMC

Chen C, Li T, Li Y, Chen Z, Shi P et al (2024a) GPX4 is a potential diagnostic and therapeutic biomarker associated with diffuse large B lymphoma cell proliferation and B cell immune infiltration. Heliyon 10(3):e24857. https://doi.org/10.1016/j.heliyon.2024.e24857 PubMed DOI PMC

Chen Y, Yang W, Cui X, Zhang H, Li L, Fu J, Guo H (2024b) Research progress on the mechanism, monitoring, and prevention of cardiac injury caused by antineoplastic drugs—anthracyclines. Biology 13(9):689. https://doi.org/10.3390/biology13090689 PubMed DOI PMC

Cheng G, Diebold BA, Hughes Y, Lambeth JD (2006) Nox1-dependent reactive oxygen generation is regulated by Rac1. J Biol Chem 281(26):17718–17726. https://doi.org/10.1074/jbc.M512751200 PubMed DOI

Cheng CW, Kuo CY, Fan CC, Fang WC et al (2013) Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species. Cell Death Dis 20:e681. https://doi.org/10.1038/cddis.2013.204 DOI

Chepelev NL, Kennedy DA, Gagné R, White T (2015) HPLC measurement of the DNA oxidation biomarker, 8-oxo-7,8-dihydro-2’-deoxyguanosine, in cultured cells and animal tissues. J Vis Exp 102:e52697. https://doi.org/10.3791/52697 DOI

Cheung EC, Vousden KH (2022) The role of ROS in tumour development and progression. Nat Rev Cancer 22(5):280–297. https://doi.org/10.1038/s41568-021-00435-0 PubMed DOI

Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, Vousden KH (2020) Dynamic ROS control by TIGAR regulates the initiation and progression of pancreatic cancer. Cancer Cell 37(2):168-182.e4. https://doi.org/10.1016/j.ccell.2019.12.012 PubMed DOI PMC

Chio IIC, Tuveson DA (2017) ROS in cancer: the burning question. Trends Mol Med 23(5):411–429. https://doi.org/10.1016/j.molmed.2017.03.004 PubMed DOI PMC

Chiorcea-Paquim AM (2022) 8-oxoguanine and 8-oxodeoxyguanosine biomarkers of oxidative DNA damage: a review on HPLC-ECD determination. Molecules 27(5):1620. https://doi.org/10.3390/molecules27051620 PubMed DOI PMC

Chourasia AH, Tracy K, Frankenberger C, Boland ML et al (2015) Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis. EMBO Rep 16(9):1145–1163. https://doi.org/10.15252/embr.201540759 PubMed DOI PMC

Chu FF, Esworthy RS, Chu PG, Longmate JA, Huycke MM, Wilczynski S, Doroshow JH (2004) Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res 64(3):962–968. https://doi.org/10.1158/0008-5472.can-03-2272 PubMed DOI

Chuang CH, Sheu BS, Kao AW, Cheng HC et al (2007) Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. Hepatogastroenterology 54(73):320–324 PubMed

Chung-man HJ, Zheng S, Comhair SA, Farver C, Erzurum SC (2001) Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res 61:8578–8585

Clare CE, Brassington AH, Kwong WY, Sinclair KD (2019) One-carbon metabolism: linking nutritional biochemistry to epigenetic programming of long-term development. Annu Rev Anim Biosci 7:263–287. https://doi.org/10.1146/annurev-animal-020518-115206 PubMed DOI

Cooper GM (2000) The cell: a molecular approach, 2nd edn. ASM Press, Washington (DC)

Cullen JJ, Mitros FA, Oberley LW (2003) Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer. Pancreas 26:23–27. https://doi.org/10.1097/00006676-200301000-00005 PubMed DOI

Davison CA, Durbin SM, Thau MR, Zellmer VR et al (2013) Antioxidant enzymes mediate survival of breast cancer cells deprived of extracellular matrix. Cancer Res 73(12):3704–3715. https://doi.org/10.1158/0008-5472.CAN-12-2482 PubMed DOI

de Almeida AJPO, de Oliveira JCPL, da Silva Pontes LV, de Souza Júnior JF et al (2022) ROS: basic concepts, sources, cellular signaling, and its implications in aging pathways. Oxid Med Cell Longev 2022:1225578. https://doi.org/10.1155/2022/1225578 PubMed DOI PMC

DeNicola GM, Karreth FA, Humpton TJ et al (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475(7354):106–109. https://doi.org/10.1038/nature10189 PubMed DOI PMC

Denniss A, Dulhunty AF, Beard NA (2018) Ryanodine receptor Ca PubMed DOI

Diehn M, Cho RW, Lobo NA et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239):780–783. https://doi.org/10.1038/nature07733 PubMed DOI PMC

Dixon SJ, Olzmann JA (2024) The cell biology of ferroptosis. Nat Rev Mol Cell Biol 25:424–442. https://doi.org/10.1038/s41580-024-00703-5 PubMed DOI PMC

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072. https://doi.org/10.1016/j.cell.2012.03.042 PubMed DOI PMC

Dizdaroglu M (1994) Chemical determination of oxidative DNA damage by gas chromatography-mass spectrometry. Meth Enzymol 234:3–16 DOI

Dizdaroglu M (2012) Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett 327(1–2):26–47. https://doi.org/10.1016/j.canlet.2012.01.016 PubMed DOI

Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H (2002) Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med 32(11):1102–1115. https://doi.org/10.1016/s0891-5849(02)00826-2 PubMed DOI

Dodson M, Castro-Portuguez R, Zhang DD (2019) NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 23:101107. https://doi.org/10.1016/j.redox.2019.101107 PubMed DOI PMC

Dong H, Markovic SN (2018) The basics of cancer immunotherapy. Springer. https://doi.org/10.1007/978-3-319-70622-1 DOI

Drakos E, Leventaki V, Schlette EJ, Jones D, Lin P, Medeiros LJ, Rassidakis GZ (2007) C-jun expression and activation are restricted to CD30+ lymphoproliferative disorders. Am J Surg Pathol 31(3):447–453. https://doi.org/10.1097/01.pas.0000213412.25935.e4 PubMed DOI

Eferl R, Wagner EF (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3(11):859–868. https://doi.org/10.1038/nrc1209 PubMed DOI

Ekoue DN, He C, Diamond AM (1858) Bonini MG (2017) Manganese superoxide dismutase and glutathione peroxidase-1 contribute to the rise and fall of mitochondrial reactive oxygen species which drive oncogenesis. Biochim Biophys Acta Bioenerg 8:628–632. https://doi.org/10.1016/j.bbabio.2017.01.006 DOI

Eliassen AH, Hendrickson SJ, Brinton LA, Buring JE et al (2012) Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst 104(24):1905–1916. https://doi.org/10.1093/jnci/djs461 PubMed DOI PMC

Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia M et al (2007) Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control. Clin Cancer Res 13(12):3637–3641. https://doi.org/10.1158/1078-0432.CCR-06-2095 PubMed DOI

Fan X, Li A, Yan Z, Geng X, Lian L, Lv H, Gao D, Zhang J (2022) From iron metabolism to ferroptosis: pathologic changes in coronary heart disease. Oxid Med Cell Longev 2022:6291889. https://doi.org/10.1155/2022/6291889 PubMed DOI PMC

Fares J, Fares MY, Khachfe HH et al (2020) Molecular principles of metastasis: a hallmark of cancer revisited. Sig Transduct Target Ther 5:28. https://doi.org/10.1038/s41392-020-0134-x DOI

Fleury C, Mignotte B, Vayssière JL (2002) Mitochondrial reactive oxygen species in cell death signaling. Biochimie 84(2–3):131–141. https://doi.org/10.1016/s0300-9084(02)01369-x PubMed DOI

Focsan AL, Polyakov NE, Kispert LD (2021) Carotenoids: importance in daily life—insight gained from EPR and ENDOR. Appl Magn Reson 52:1093–1112. https://doi.org/10.1007/s00723-021-01311-8 PubMed DOI PMC

Forman HJ, Zhang H, Rinna A (2009) Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 30(1–2):1–12. https://doi.org/10.1016/j.mam.2008.08.006 PubMed DOI

Forshaw TE, Holmila R, Nelson KJ, Lewis JE, Kemp ML et al (2019) Peroxiredoxins in cancer and response to radiation therapies. Antioxidants 8(1):11. https://doi.org/10.3390/antiox8010011 PubMed DOI PMC

Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837. https://doi.org/10.1093/eurheartj/ehr304 PubMed DOI

Fouad YA, Aanei C (2017) Revisiting the hallmarks of cancer. Am J Cancer Res 7(5):1016–1036 PubMed PMC

Franklin CC, Backos DS, Mohar I, White CC, Forman HJ, Kavanagh TJ (2009) Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Mol Aspects Med 30(1–2):86–98. https://doi.org/10.1016/j.mam.2008.08.009 PubMed DOI

Fukai T, Ushio-Fukai M (2020) Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells 9(8):1849. https://doi.org/10.3390/cells9081849 PubMed DOI PMC

Galasso M, Gambino S, Romanelli MG, Donadelli M, Scupoli MT (2021) Browsing the oldest antioxidant enzyme: catalase and its multiple regulation in cancer. Free Radic Biol Med 172:264–272. https://doi.org/10.1016/j.freeradbiomed.2021.06.010 PubMed DOI

Gan X, Chen B, Shen Z, Liu Y et al (2014) High GPX1 expression promotes esophageal squamous cell carcinoma invasion, migration, proliferation and cisplatin-resistance but can be reduced by vitamin D. Int J Clin Exp Med 7(9):2530–2540 PubMed PMC

Gann PH, Deaton RJ, Rueter EE, van Breemen RB et al (2015) A phase II randomized trial of lycopene-rich tomato extract among men with high-grade prostatic intraepithelial neoplasia. Nutr Cancer 67(7):1104–1112. https://doi.org/10.1080/01635581.2015.1075560 PubMed DOI PMC

Gansemer ER, McCommis KS, Martino M, King-McAlpin AQ et al (2020) NADPH and glutathione redox link TCA cycle activity to endoplasmic reticulum homeostasis. iScience 23(5):101116. https://doi.org/10.1016/j.isci.2020.101116 PubMed DOI PMC

Gao H, Nepovimova E, Heger Z, Valko M, Wu Q, Kuca K, Adam V (2023) Role of hypoxia in cellular senescence. Pharmacol Res 194:106841. https://doi.org/10.1016/j.phrs.2023.106841 PubMed DOI

Gazon H, Barbeau B, Mesnard JM, Peloponese JM Jr (2018) Hijacking of the AP-1 signaling pathway during development of ATL. Front Microbiol 8:2686. https://doi.org/10.3389/fmicb.2017.02686 PubMed DOI PMC

Gianni D, Diaz B, Taulet N, Fowler B, Courtneidge SA, Bokoch GM (2009) Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity. Sci Signal 2(88):ra54. https://doi.org/10.1126/scisignal.2000370 PubMed DOI PMC

Gibellini L, Losi L, De Biasi S, Nasi M et al (2018) LonP1 differently modulates mitochondrial function and bioenergetics of primary versus metastatic colon cancer cells. Front Oncol 8:254. https://doi.org/10.3389/fonc.2018.00254 PubMed DOI PMC

Gill JG, Piskounova E, Morrison SJ (2016) Cancer, oxidative stress, and metastasis. Cold Spring Harb Symp Quant Biol 81:163–175. https://doi.org/10.1101/sqb.2016.81.030791 PubMed DOI

Giovannucci E (2002) A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood) 227(10):852–859. https://doi.org/10.1177/153537020222701003 PubMed DOI

Glasauer A, Sena LA, Diebold LP, Mazar AP, Chandel NS (2014) Targeting SOD1 reduces experimental non–small-cell lung cancer. J Clin Invest 124(1):117–128. https://doi.org/10.1172/JCI71714 PubMed DOI

Glorieux C, Calderon PB (2017) Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol Chem 398(10):1095–1108. https://doi.org/10.1515/hsz-2017-0131 PubMed DOI

Glorieux C, Sandoval JM, Fattaccioli A, Dejeans N et al (2016) Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress. Free Radic Biol Med 99:436–450. https://doi.org/10.1016/j.freeradbiomed.2016.08.031 PubMed DOI

Glorieux C, Liu S, Trachootham D, Huang P (2024) Targeting ROS in cancer: rationale and strategies. Nat Rev Drug Discov 23(8):583–606. https://doi.org/10.1038/s41573-024-00979-4 PubMed DOI

Godet I, Shin YJ, Ju JA, Ye IC, Wang G, Gilkes DM (2019) Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat Commun 10(1):4862. https://doi.org/10.1038/s41467-019-12412-1 PubMed DOI PMC

Goh J, Enns L, Fatemie S et al (2011) Mitochondrial targeted catalase suppresses invasive breast cancer in mice. BMC Cancer 11:191. https://doi.org/10.1186/1471-2407-11-191 PubMed DOI PMC

Gontero P, Marra G, Soria F, Oderda M et al (2015) A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. chemoprevention or “chemopromotion”? Prostate 75(11):1177–1186. https://doi.org/10.1002/pros.22999 PubMed DOI

Gorkom GNY, Lookermans EL, Van Elssen CHMJ, Bos GMJ (2019) The effect of vitamin C (ascorbic acid) in the treatment of patients with cancer: a systematic review. Nutrients 11(5):977. https://doi.org/10.3390/nu11050977 PubMed DOI PMC

Görlach A, Bertram K, Hudecova S, Krizanova O (2015) Calcium and ROS: a mutual interplay. Redox Biol 6:260–271. https://doi.org/10.1016/j.redox.2015.08.010 PubMed DOI PMC

Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12(12):931–947. https://doi.org/10.1038/nrd4002 PubMed DOI

Griess B, Tom E, Domann F et al (2017) Extracellular superoxide dismutase and its role in cancer. Free Radic Biol Med 112:464–479. https://doi.org/10.1016/j.freeradbiomed.2017.08.013 PubMed DOI PMC

Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M (2023) Targeting DNA damage response pathways in cancer. Nat Rev Cancer 23(2):78–94. https://doi.org/10.1038/s41568-022-00535-5 PubMed DOI

Gu MM, Gao D, Yao PA, Yu L et al (2018) P53-inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma. Cancer Sci 109(12):3783–3793. https://doi.org/10.1111/cas.13818 PubMed DOI PMC

Guerriero E, Capone F, Accardo M, Sorice A et al (2015) GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues. Eur J Histochem 59(4):2540. https://doi.org/10.4081/ejh.2015.2540 PubMed DOI PMC

Haddad AQ, Venkateswaran V, Viswanathan L, Teahan SJ et al (2006) Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis 9(1):68–76. https://doi.org/10.1038/sj.pcan.4500845 PubMed DOI

Hahm JY, Park J, Jang ES et al (2022) 8-oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification. Exp Mol Med 54:1626–1642. https://doi.org/10.1038/s12276-022-00822-z PubMed DOI PMC

Halliwell B (2022) Reactive oxygen species (ROS), oxygen radicals and antioxidants: where are we now, where is the field going and where should we go? Biochem Biophys Res Commun 633:17–19. https://doi.org/10.1016/j.bbrc.2022.08.098 PubMed DOI

Halliwell B, Gutteridge JMC (2015) Free radicals in biology and medicine. Oxford University Press. https://doi.org/10.1093/acprof:oso/9780198717478.001.0001 DOI

Hampton MB, Vick KA, Skoko JJ, Neumann CA (2018) Peroxiredoxin involvement in the initiation and progression of human cancer. Antioxid Redox Signal 28(7):591–608. https://doi.org/10.1089/ars.2017.7422 PubMed DOI PMC

Han J, Sun P (2007) The pathways to tumor suppression via route p38. Trends Biochem Sci 32(8):364–371. https://doi.org/10.1016/j.tibs.2007.06.007 PubMed DOI

Han Y, Liu D, Li L (2020) PD-1/PD-L1 pathway: current research in cancer. Am J Cancer Res 10(3):727–742 PubMed PMC

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013 PubMed DOI

Hansen R, Sæbø M, Skjelbred CF, Nexø BA et al (2005) GPX pro198Leu and OGG1 ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett 229:85–91. https://doi.org/10.1016/j.canlet.2005.04.019 PubMed DOI

Harris IS, Treloar AE, Inoue S, Sasaki M et al (2015) Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 27(2):211–122. https://doi.org/10.1016/j.ccell.2014.11.019 PubMed DOI

Hashinokuchi A, Matsubara T, Ono Y, Shunichi S et al (2024) Clinical and prognostic significance of glutathione peroxidase 2 in lung adenocarcinoma. Ann Surg Oncol 31(7):4822–4829. https://doi.org/10.1245/s10434-024-15116-z PubMed DOI

Hawk MA, Gorsuch CL, Fagan P, Lee C et al (2018) C RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells. Nat Cell Biol 20(3):272–284. https://doi.org/10.1038/s41556-018-0034-2 PubMed DOI

Hayes P, Knaus UG (2013) Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and perpetrator. Antioxid Redox Signal 18(15):1937–1945. https://doi.org/10.1089/ars.2012.4895 PubMed DOI

Hayes JD, Dinkova-Kostova AT, Tew KD (2020) Oxidative stress in cancer. Cancer Cell 38(2):167–197. https://doi.org/10.1016/j.ccell.2020.06.001 PubMed DOI PMC

He Q, Chen N, Wang X, Li P et al (2023) Prognostic value and immunological roles of GPX3 in gastric cancer. Int J Med Sci 20(11):1399–1416. https://doi.org/10.7150/ijms.85253 PubMed DOI PMC

Hecht F, Zocchi M, Alimohammadi F, Harris IS (2024) Regulation of antioxidants in cancer. Mol Cell 84(1):23–33. https://doi.org/10.1016/j.molcel.2023.11.001 PubMed DOI

Heinonen OP, Albanes D, Virtamo J, Taylor PR et al (1998) Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90(6):440–446. https://doi.org/10.1093/jnci/90.6.440 PubMed DOI

Hemachandra LP, Shin DH, Dier U, Iuliano JN et al (2015) Mitochondrial superoxide dismutase has a protumorigenic role in ovarian clear cell carcinoma. Cancer Res 75(22):4973–4984. https://doi.org/10.1158/0008-5472.CAN-14-3799 PubMed DOI PMC

Hempel N, Ye H, Abessi B, Mian B, Melendez JA (2009) Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic Biol Med 46(1):42–50. https://doi.org/10.1016/j.freeradbiomed.2008.09.020 PubMed DOI

Hernández Borrero LJ, El-Deiry WS (2021) Tumor suppressor p53: biology, signaling pathways, and therapeutic targeting. Biochim Biophys Acta (BBA) 1876(1):188556. https://doi.org/10.1016/j.bbcan.2021.188556 DOI

Higdon J, Drake VJ, Delage B, Crozier A (2016). Flavonoids, Linus Pauling Institute, Oregon State University, https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids#reference134 Accessed 5 Dec 2024

Higdon J, Drake VJ, Delage B, Johnson EJ (2023). Carotenoids, linus pauling institute, oregon state University, https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/carotenoids#reference63 Accessed 5 Dec 2024

Higdon J, Drake VJ, Delage B, Traber MG (2024) Vitamin E, Linus Pauling Institute, Oregon State University, https://lpi.oregonstate.edu/mic/vitamins/vitamin-E Accessed 5 Dec 2024

Hjelmeland AB, Patel RP (2019) SOD2 acetylation and deacetylation: another tale of Jekyll and Hyde in cancer. Proc Natl Acad Sci U S A 116(47):23376–23378. https://doi.org/10.1073/pnas.1916214116 PubMed DOI PMC

Horn A, Raavicharla S, Shah S, Cox D, Jaiswal JK (2020) Mitochondrial fragmentation enables localized signaling required for cell repair. J Cell Biol 219(5):e201909154. https://doi.org/10.1083/jcb.201909154 PubMed DOI PMC

Hu J, Zhou G, Wang N, Wang Y (2010) GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 124:425–431. https://doi.org/10.1007/s10549-010-0841-z PubMed DOI

Hu Q, Chen J, Yang W, Xu M, Zhou J, Tan J, Huang T (2023) GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers. Front Oncol 13:990551. https://doi.org/10.3389/fonc.2023.990551 PubMed DOI PMC

Huang Z, Liu Y, Huang Z, Li H, Gan X, Shen Z (2016) 1,25-dihydroxyvitamin D3 alleviates salivary adenoid cystic carcinoma progression by suppressing GPX1 expression through the NF-κB pathway. Int J Oncol 48(3):1271–1279. https://doi.org/10.3892/ijo.2016.3341 PubMed DOI

Huang L, Guo Z, Wang F et al (2021a) KRAS mutation: from undruggable to druggable in cancer. Sig Transduct Target Ther 6:386. https://doi.org/10.1038/s41392-021-00780-4 DOI

Huang R, Chen H, Liang J, Li Y et al (2021b) Dual role of reactive oxygen species and their application in cancer therapy. J Cancer 12(18):5543–5561. https://doi.org/10.7150/jca.54699 PubMed DOI PMC

Humpton TJ, Vousden KH (2016) Regulation of cellular metabolism and hypoxia by p53. Cold Spring Harb Perspect Med 6:a026146. https://doi.org/10.1101/cshperspect.a026146 PubMed DOI PMC

Humpton TJ, Hock AK, Maddocks ODK et al (2018) P53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant. Cancer Metab 6:18. https://doi.org/10.1186/s40170-018-0191-6 PubMed DOI PMC

Huo Y, Yin S, Yan M, Win S (2017) Protective role of p53 in acetaminophen hepatotoxicity. Free Radic Biol Med 106:111–117. https://doi.org/10.1016/j.freeradbiomed.2017.02.028 PubMed DOI PMC

Hwang TS, Choi HK, Han HS (2007) Differential expression of manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase in gastric adenocarcinoma and normal gastric mucosa. Eur J Surg Oncol 33:474–479. https://doi.org/10.1016/j.ejso.2006.10.024 PubMed DOI

Ichijo H, Nishida E, Irie K et al (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275(5296):90–94. https://doi.org/10.1126/science.275.5296.90 PubMed DOI

Igelmann S, Neubauer HA, Ferbeyre G (2019) STAT3 and STAT5 activation in solid cancers. Cancers (Basel) 11(10):1428. https://doi.org/10.3390/cancers11101428 PubMed DOI

Imyanitov EN, Togo AV, Hanson KP (2004) Searching for cancer-associated gene polymorphisms: promises and obstacles. Cancer Lett 204(1):3–14. https://doi.org/10.1016/j.canlet.2003.09.026 PubMed DOI

Iqbal MJ, Kabeer A, Abbas Z et al (2024) Interplay of oxidative stress, cellular communication and signaling pathways in cancer. Cell Commun Signal 22:7. https://doi.org/10.1186/s12964-023-01398-5 PubMed DOI PMC

Ishikawa F, Kaneko E, Sugimoto T et al (2014) A mitochondrial thioredoxin-sensitive mechanism regulates TGF-β-mediated gene expression associated with epithelial-mesenchymal transition. Biochem Biophys Res Commun 443(3):821–827. https://doi.org/10.1016/j.bbrc.2013.12.050 PubMed DOI

Islinger M, Voelkl A, Fahimi HD, Schrader M (2018) The peroxisome: an update on mysteries 2.0. Histochem Cell Biol 150(5):443–471. https://doi.org/10.1007/s00418-018-1722-5 PubMed DOI PMC

Janaszak-Jasiecka A, Płoska A, Wierońska JM et al (2023) Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets. Cell Mol Biol Lett 28(1):21. https://doi.org/10.1186/s11658-023-00423-2 PubMed DOI PMC

Jaruga P, Rodriguez H, Dizdaroglu M (2001) Measurement of 8-hydroxy-2’-deoxyadenosine in DNA by liquid chromatography/mass spectrometry. Free Radic Biol Med 31(3):336–344. https://doi.org/10.1016/s0891-5849(01)00594-9 PubMed DOI

Jassim A, Rahrmann EP, Simons BD, Gilbertson RJ (2023) Cancers make their own luck: theories of cancer origins. Nat Rev Cancer 23(10):710–724. https://doi.org/10.1038/s41568-023-00602-5 PubMed DOI

Jiang L, Kon N, Li T et al (2015) Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520:57–62. https://doi.org/10.1038/nature14344 PubMed DOI PMC

Jiang J, Wang K, Chen Y et al (2017) Redox regulation in tumor cell epithelial–mesenchymal transition: molecular basis and therapeutic strategy. Sig Transduct Target Ther 2:17036. https://doi.org/10.1038/sigtrans.2017.36 DOI

Jin M, Wang J, Ji X, Cao H et al (2019) Mcur1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma. J Exp Clin Cancer Res 38(1):136. https://doi.org/10.1186/s13046-019-1135-x PubMed DOI PMC

Jomova K, Valko M (2013) Health protective effects of carotenoids and their interactions with other biological antioxidants. Eur J Med Chem 70:102–110. https://doi.org/10.1016/j.ejmech.2013.09.054 PubMed DOI

Jomova K, Hudecova L, Lauro P, Simunkova M, Alwasel SH, Alhazza IM, Valko M (2019) A switch between antioxidant and prooxidant properties of the phenolic compounds myricetin, morin, 3’,4’-dihydroxyflavone, taxifolin and 4-hydroxy-coumarin in the presence of copper(II) ions: a spectroscopic, absorption titration and DNA damage study. Molecules 24(23):4335. https://doi.org/10.3390/molecules24234335 PubMed DOI PMC

Jomova K, Makova M, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Rhodes CJ, Valko M (2022) Essential metals in health and disease. Chem Biol Interact 367:110173. https://doi.org/10.1016/j.cbi.2022.110173 PubMed DOI

Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M (2023) Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol 97(10):2499–2574. https://doi.org/10.1007/s00204-023-03562-9 PubMed DOI PMC

Jomova K, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M (2024) Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol 98(5):1323–1367. https://doi.org/10.1007/s00204-024-03696-4 PubMed DOI PMC

Jomova K, Alomar SY, Valko R, Liska J, Nepovimova E, Kuca K, Valko M (2025) Flavonoids and their role in oxidative stress, inflammation, and human diseases. Chem Biol Interact 413:111489. https://doi.org/10.1016/j.cbi.2025.111489 PubMed DOI

Ju HQ, Lin JF, Tian T et al (2020) NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications. Sig Transduct Target Ther 5:231. https://doi.org/10.1038/s41392-020-00326-0 DOI

Juarez JC, Manuia M, Burnett ME, Betancourt O, Boivin B, Shaw DE, Tonks NK, Mazar AP, Doñate F (2008) Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling. Proc Natl Acad Sci U S A 105(20):7147–7152. https://doi.org/10.1073/pnas.0709451105 PubMed DOI PMC

Kalinina E (2024) Glutathione-dependent pathways in cancer cells. Int J Mol Sci 25:8423. https://doi.org/10.3390/ijms25158423 PubMed DOI PMC

Kang MY, Kim HB, Piao C, Lee KH et al (2013) The critical role of catalase in prooxidant and antioxidant function of p53. Cell Death Differ 20(1):117–129. https://doi.org/10.1038/cdd.2012.102 PubMed DOI

Kant M, Akış M, Çalan M, Arkan T, Bayraktar F, Dizdaroglu M, İşlekel H (2016) Elevated urinary levels of 8-oxo-2’-deoxyguanosine, (5’R)- and (5’S)-8,5’-cyclo-2’-deoxyadenosines, and 8-iso-prostaglandin F PubMed DOI

Karlenius TC, Tonissen KF (2010) Thioredoxin and cancer: a role for thioredoxin in all states of tumor oxygenation. Cancers (Basel) 2(2):209–232. https://doi.org/10.3390/cancers2020209 PubMed DOI

Kataja-Tuomola MK, Kontto JP, Männistö S, Albanes D, Virtamo JR (2010) Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: results of the ATBC study. Ann Med 42(3):178–186. https://doi.org/10.3109/07853890903508887 PubMed DOI

Kennedy L, Sandhu JK, Harper ME, Cuperlovic-Culf M (2020) Role of glutathione in cancer: from mechanisms to therapies. Biomolecules 10(10):1429. https://doi.org/10.3390/biom10101429 PubMed DOI PMC

Kennel KB, Greten FR (2021) Immune cell - produced ROS and their impact on tumor growth and metastasis. Redox Biol 42:101891. https://doi.org/10.1016/j.redox.2021.101891 PubMed DOI PMC

Kharman-Biz A, Gao H, Ghiasvand R, Zhao C, Zendehdel K, Dahlman-Wright K (2013) Expression of activator protein-1 (AP-1) family members in breast cancer. BMC Cancer 13:441. https://doi.org/10.1186/1471-2407-13-441 PubMed DOI PMC

Khatib A, Solaimuthu B, Ben Yosef M, Abu Rmaileh A et al (2020) The glutathione peroxidase 8 (GPX8)/IL-6/STAT3 axis is essential in maintaining an aggressive breast cancer phenotype. Proc Natl Acad Sci U S A 117(35):21420–21431. https://doi.org/10.1073/pnas.2010275117 PubMed DOI PMC

Kim SY, Kwon OJ, Park JW (2001) Inactivation of catalase and superoxide dismutase by singlet oxygen derived from photoactivated dye. Biochimie 83(5):437–444. https://doi.org/10.1016/s0300-9084(01)01258-5 PubMed DOI

Kim J, Mizokami A, Shin M, Izumi K et al (2014) SOD3 acts as a tumor suppressor in PC-3 prostate cancer cells via hydrogen peroxide accumulation. Anticancer Res 34(6):2821–2831 PubMed

Kim YS, Gupta Vallur P, Phaëton R, Mythreye K, Hempel N (2017) Insights into the dichotomous regulation of SOD2 in cancer. Antioxidants 6(4):86. https://doi.org/10.3390/antiox6040086 PubMed DOI PMC

Kincaid B, Bossy-Wetzel E (2013) Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration. Front Aging Neurosci 5:48. https://doi.org/10.3389/fnagi.2013.00048 PubMed DOI PMC

Klein CA (2013) Selection and adaptation during metastatic cancer progression. Nat 501(7467):365–372. https://doi.org/10.1038/nature12628 DOI

Kobayashi EH, Suzuki T, Funayama R et al (2016) Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 7:11624. https://doi.org/10.1038/ncomms11624 PubMed DOI PMC

Koch A, Ebert EV, Seitz T, Dietrich P, Berneburg M, Bosserhoff A, Hellerbrand C (2020) Characterization of glycolysis-related gene expression in malignant melanoma. Pathol Res Pract 216(1):152752. https://doi.org/10.1016/j.prp.2019.152752 PubMed DOI

Kong H, Reczek CR, McElroy GS, Steinert EM, Wang T, Sabatini DM, Chandel MS (2020) Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species. Sci Adv 6(45):eabb7272. https://doi.org/10.1126/sciadv.abb7272 PubMed DOI PMC

König S, Strassheimer F, Brandner NI, Schröder JH et al (2024) Superoxide dismutase 1 mediates adaptation to the tumor microenvironment of glioma cells via mammalian target of rapamycin complex 1. Cell Death Discov 10(1):379. https://doi.org/10.1038/s41420-024-02145-6 PubMed DOI PMC

Kotla NK, Dutta P, Parimi S, Das NK (2022) The role of ferritin in health and disease: recent advances and understandings. Metabolites 12(7):609. https://doi.org/10.3390/metabo12070609 PubMed DOI PMC

Kovac S, Angelova PR, Holmström KM, Zhang Y, Dinkova-Kostova AT, Abramov AY (2015) Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim Biophys Acta 1850(4):794–801. https://doi.org/10.1016/j.bbagen.2014.11.021 PubMed DOI PMC

Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, Vercesi AE (2009) Mitochondria and reactive oxygen species. Free Radic Biol Med 47(4):333–343. https://doi.org/10.1016/j.freeradbiomed.2009.05.004 PubMed DOI

Krajewska B, Brindell M (2011) Urease activity and L-ascorbic acid. J Enzyme Inhib Med Chem 26(3):309–318. https://doi.org/10.3109/14756366.2010.504675 PubMed DOI

Krinsky NI, Landrum JT, Bone RA (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr 23:171–201. https://doi.org/10.1146/annurev.nutr.23.011702.073307 PubMed DOI

Kristal AR, Darke AK, Morris JS, Tangen CM et al (2014) Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst 106(3):djt456. https://doi.org/10.1093/jnci/djt456 PubMed DOI PMC

Krylatov AV, Maslov LN, Voronkov NS et al (2018) Reactive oxygen species as intracellular signaling molecules in the cardiovascular system. Curr Cardiol Rev 14(4):290–300. https://doi.org/10.2174/1573403X14666180702152436 PubMed DOI PMC

Kryston TB, Georgiev AB, Pissis P, Georgakilas AG (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 711(1–2):193–201. https://doi.org/10.1016/j.mrfmmm.2010.12.016 PubMed DOI

Kuo CL, Chou HY, Chiu YC, Cheng AN et al (2020) Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Lett 474:138–150. https://doi.org/10.1016/j.canlet.2020.01.019 PubMed DOI

Kuo CL, Ponneri Babuharisankar A, Lin YC et al (2022) Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend? J Biomed Sci 29:74. https://doi.org/10.1186/s12929-022-00859-2 PubMed DOI PMC

Labuschagne CF, Cheung EC, Blagih J, Domart MC, Vousden KH (2019) Cell clustering promotes a metabolic switch that supports metastatic colonization. Cell Metab 30(4):720-734.e5. https://doi.org/10.1016/j.cmet.2019.07.014 PubMed DOI PMC

Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15(3):178–196. https://doi.org/10.1038/nrm3758 PubMed DOI PMC

Lane DP (1992) p53, guardian of the genome. Nature 358(6381):15–16. https://doi.org/10.1038/358015a0 PubMed DOI

Lash LH (2006) Mitochondrial glutathione transport: physiological, pathological and toxicological implications. Chem Biol Interact 163(1–2):54–67. https://doi.org/10.1016/j.cbi.2006.03.001 PubMed DOI PMC

Lauer C, Volkl A, Riedl S, Fahimi HD, Beier K (1999) Impairment of peroxisomal biogenesis in human colon carcinoma. Carcinogenesis 20:985–989. https://doi.org/10.1093/carcin/20.6.985 PubMed DOI

Le Gal K, Ibrahim MX, Wiel C, Sayin VI et al (2015a) Antioxidants can increase melanoma metastasis in mice. Sci Transl Med 7(308):308re8. https://doi.org/10.1126/scitranslmed.aad3740 PubMed DOI

Le Gal K, Ibrahim MX, Wiel C, Sayin VI et al (2015b) Antioxidants can increase melanoma metastasis in mice. Sci Transl Med 7(308):308–318. https://doi.org/10.1126/scitranslmed.aad3740 DOI

Lee W, Jiang Z, Liu J et al (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465(7297):473–477. https://doi.org/10.1038/nature09004 PubMed DOI

Lee JR, Roh JL, Lee SM, Park Y, Cho KJ, Nam SY, Kim SY (2017) Overexpression of glutathione peroxidase 1 predicts poor prognosis in oral squamous cell carcinoma. J Cancer Res Clin Oncol 143(11):2257-2265. https://doi.org/10.1007/s00432-017-2466-7 PubMed DOI PMC

Lee HY, Kim HK, Hoang TH, Yang S, Kim HR, Chae HJ (2020) The correlation of IRE1α oxidation with Nox4 activation in aging-associated vascular dysfunction. Redox Biol 37:101727. https://doi.org/10.1016/j.redox.2020.101727 PubMed DOI PMC

Li Y, Liang R, Zhang X, Wang J (2019) Copper chaperone for superoxide dismutase promotes breast cancer cell proliferation and migration via ROS-mediated MAPK/ERK signaling. Front Pharmacol 10:356. https://doi.org/10.3389/fphar.2019.00356 PubMed DOI PMC

Li J, Wang XH, Hu J, Shi M, Zhang L, Chen H (2020a) Combined treatment with N-acetylcysteine and gefitinib overcomes drug resistance to gefitinib in NSCLC cell line. Cancer Med 9(4):1495–1502. https://doi.org/10.1002/cam4.2610 PubMed DOI

Li K, Liu T, Chen J et al (2020b) Survivin in breast cancer–derived exosomes activates fibroblasts by up-regulating SOD1, whose feedback promotes cancer proliferation and metastasis. J Biol Chem 295:13737–13752. https://doi.org/10.1074/jbc.RA120.013805 PubMed DOI PMC

Lignitto L, LeBoeuf SE, Homer H, Jiang S et al (2019) Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1. Cell 178(2):316-329.e18. https://doi.org/10.1016/j.cell.2019.06.003 PubMed DOI PMC

Lim SO, Gu JM, Kim MS, Kim HS et al (2008) Epigenetic changes induced by reactive oxygen species in hepatocellular carcinoma: methylation of the E-cadherin promoter. Gastroenterology 135(6):2128–2140. https://doi.org/10.1053/j.gastro.2008.07.027 PubMed DOI

Lin D, Shen L, Luo M et al (2021) Circulating tumor cells: biology and clinical significance. Sig Transduct Target Ther 6:404. https://doi.org/10.1038/s41392-021-00817-8 DOI

Liu C, Russell RM (2008) Nutrition and gastric cancer risk: an update. Nutr Rev 66(5):237–249. https://doi.org/10.1111/j.1753-4887.2008.00029.x PubMed DOI

Liu Q, Bai W, Huang F, Tang J, Lin X (2019) Downregulation of microRNA-196a inhibits stem cell self-renewal ability and stemness in non-small-cell lung cancer through upregulating GPX3 expression. Int J Biochem Cell Biol 115:105571. https://doi.org/10.1016/j.biocel.2019.105571 PubMed DOI

Liu S, Li B, Xu J, Hu S et al (2020a) SOD1 promotes cell proliferation and metastasis in non-small cell lung cancer via an miR-409-3p/SOD1/SETDB1 epigenetic regulatory feedforward loop. Front Cell Dev Biol 8:213. https://doi.org/10.3389/fcell.2020.00213 PubMed DOI PMC

Liu X, Fan L, Lu C, Yin S, Hu H (2020b) Functional role of p53 in the regulation of chemical-induced oxidative stress. Oxid Med Cell Longev 2020:6039769. https://doi.org/10.1155/2020/6039769 PubMed DOI PMC

Lozhkin A, Vendrov AE, Pan H, Wickline SA, Madamanchi NR, Runge MS (2017) NADPH oxidase 4 regulates vascular inflammation in aging and atherosclerosis. J Mol Cell Cardiol 102:10–21. https://doi.org/10.1016/j.yjmcc.2016.12.004 PubMed DOI

Luo C, Lim JH, Lee Y, Granter SR et al (2016) A PGC1α-mediated transcriptional axis suppresses melanoma metastasis. Nature 537(7620):422–426. https://doi.org/10.1038/nature19347 PubMed DOI PMC

Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P (2016) Nafld causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature 531(7593):253–257. https://doi.org/10.1038/nature16969 PubMed DOI PMC

Maillet A, Pervaiz S (2012) Redox regulation of p53, redox effectors regulated by p53: a subtle balance. Antioxid Redox Signal 16(11):1285–1294. https://doi.org/10.1089/ars.2011.4434 PubMed DOI

Mandl M, Depping R (2014) Hypoxia-inducible aryl hydrocarbon receptor nuclear translocator (ARNT) (HIF-1β): is it a rare exception? Mol Med 20(1):215–2120. https://doi.org/10.2119/molmed.2014.00032 PubMed DOI PMC

Marcar L, Bardhan K, Gheorghiu L et al (2019) Acquired resistance of EGFR-mutated lung cancer to tyrosine kinase inhibitor treatment promotes PARP Inhibitor sensitivity. Cell Rep 27(12):3422-3432.e4. https://doi.org/10.1016/j.celrep.2019.05.058 PubMed DOI PMC

Martínez-Reyes I, Chandel NS (2021) Cancer metabolism: looking forward. Nat Rev Cancer 21:669–680. https://doi.org/10.1038/s41568-021-00378-6 PubMed DOI

Mason JA, Hagel KR, Hawk MA, Schafer ZT et al (2017) Metabolism during ECM detachment: achilles heel of cancer cells? Trends Cancer 3(7):475–481. https://doi.org/10.1016/j.trecan.2017.04.009 PubMed DOI

McMahon M, Itoh K, Yamamoto M, Hayes JD (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 278(24):21592–21600. https://doi.org/10.1074/jbc.M300931200 PubMed DOI

Men T, Zhang X, Yang J, Shen B, Li X, Chen D, Wang J (2014) The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis. Tumor Biol 35:269–275. https://doi.org/10.1007/s13277-013-1035-1 DOI

Min JY, Lim SO, Jung G (2010) Downregulation of catalase by reactive oxygen species via hypermethylation of CpG island II on the catalase promoter. FEBS Lett 584(11):2427–2432. https://doi.org/10.1016/j.febslet.2010.04.048 PubMed DOI

Miyanaga N, Akaza H, Hinotsu S, Fujioka T et al (2012) Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 103(1):125–130. https://doi.org/10.1111/j.1349-7006.2011.02120.x PubMed DOI

Mohan C, Das C, Tyler J (2021) Histone and chromatin dynamics facilitating DNA repair. DNA Repair 107:103183. https://doi.org/10.1016/j.dnarep.2021.103183 PubMed DOI PMC

Moloney JN, Cotter TG (2018) ROS signalling in the biology of cancer. Semin Cell Dev Biol 80:50–64. https://doi.org/10.1016/j.semcdb.2017.05.023 PubMed DOI

Monaci S, Coppola F, Filippi I, Falsini A, Carraro F, Naldini A (2024) Targeting hypoxia signaling pathways in angiogenesis. Front Physiol 15:1408750. https://doi.org/10.3389/fphys.2024.1408750 PubMed DOI PMC

Moon DO, Kim MO, Choi YH, Hyun JW (2010) Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation. Cancer Lett 288(2):204–213. https://doi.org/10.1016/j.canlet.2009.07.002 PubMed DOI

Morgan MJ, Liu ZG (2011) Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 21(1):103–115. https://doi.org/10.1038/cr.2010.178 PubMed DOI

Mori K, Uchida T, Yoshie T, Mizote Y et al (2019) A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS-activated cancer cells. FEBS J 286(3):459–478. https://doi.org/10.1111/febs.14671 PubMed DOI

Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13. https://doi.org/10.1042/BJ20081386 PubMed DOI

Myant KB, Cammareri P, McGhee EJ et al (2013) ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 12(6):761–773. https://doi.org/10.1016/j.stem.2013.04.006 PubMed DOI PMC

Nakamura M, Ohsawa S, Igaki T (2014) Mitochondrial defects trigger proliferation of neighbouring cells via a senescence-associated secretory phenotype in Drosophila. Nat Commun 5:5264. https://doi.org/10.1038/ncomms6264 PubMed DOI

Nauman G, Gray JC, Parkinson R et al (2018a) Systematic review of intravenous ascorbate in cancer clinical trials. Antioxidants 7(7):89. https://doi.org/10.3390/antiox7070089 PubMed DOI PMC

Nauman G, Gray JC, Parkinson R, Levine M, Paller CJ (2018b) Systematic review of intravenous ascorbate in cancer clinical trials. Antioxidants 7(7):89. https://doi.org/10.3390/antiox7070089 PubMed DOI PMC

Nelson KK, Melendez JA (2004) Mitochondrial redox control of matrix metalloproteinases. Free Radic Biol Med 37(6):768–784. https://doi.org/10.1016/j.freeradbiomed.2004.06.008 PubMed DOI

Nelson KK, Ranganathan AC, Mansouri J, Rodriguez AM et al (2003) Elevated sod2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis. Clin Cancer Res 9(1):424–432 PubMed

Nenoi N, Ichimura S, Mita K, Yukawa O, Cartwright IL (2001) Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer Res 61:5885–5894 PubMed

Neumann CA, Krause DS, Carman CV et al (2003) Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424(6948):561–565. https://doi.org/10.1038/nature01819 PubMed DOI

Ngo V, Duennwald ML (2022) Nrf2 and oxidative stress: a general overview of mechanisms and implications in human disease. Antioxidants 11(12):2345. https://doi.org/10.3390/antiox11122345 PubMed DOI PMC

Nguyen VD, Saaranen MJ, Karala AR, Lappi AK et al (2011) Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation. J Mol Biol 406(3):503–515. https://doi.org/10.1016/j.jmb.2010.12.039 PubMed DOI

Nguyen TT, Grimm SA, Bushel PR et al (2018) Revealing a human p53 universe. Nucleic Acids Res 46(16):8153–8167. https://doi.org/10.1093/nar/gky720 PubMed DOI PMC

Nguyen TTM, Nguyen TH, Kim HS, Dao TTP et al (2023) GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT. J Exp Clin Cancer Res 42(1):42. https://doi.org/10.1186/s13046-023-02607-2 PubMed DOI PMC

Nieto MA, Huang RY, Jackson RA, Thiery JP (2016) EMT: 2016. Cell 166(1):21–45. https://doi.org/10.1016/j.cell.2016.06.028 PubMed DOI

Nimptsch K, Zhang X, Cassidy A et al (2016) Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts. Am J Clin Nutr 103(1):184–191. https://doi.org/10.3945/ajcn.115.117507 PubMed DOI

Nishikawa M (2008) Reactive oxygen species in tumor metastasis. Cancer Lett 266:53–59 PubMed DOI

Niu X, Stancliffe E, Gelman SJ, Wang L et al (2023) Cytosolic and mitochondrial NADPH fluxes are independently regulated. Nat Chem Biol 19(7):837–845. https://doi.org/10.1038/s41589-023-01283-9 PubMed DOI PMC

Nolfi-Donegan D, Braganza A, Shiva S (2020) Mitochondrial electron transport chain: oxidative phosphorylation, oxidant production, and methods of measurement. Redox Biol 37:101674. https://doi.org/10.1016/j.redox.2020.101674 PubMed DOI PMC

Oberley LW, Buettner GR (1979) Role of superoxide dismutase in cancer: a review. Cancer Res 39(4):1141–1149 PubMed

Ochoa CD, Wu RF, Terada LS (2018) ROS signaling and ER stress in cardiovascular disease. Mol Aspects Med 63:18–29. https://doi.org/10.1016/j.mam.2018.03.002 PubMed DOI PMC

Ock CY, Kim S, Keam B, Kim M et al (2016) PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget 7(13):15901–15914. https://doi.org/10.18632/oncotarget.7431 PubMed DOI PMC

Ouyang S, Zhang Q, Lou L, Zhu K, Li Z, Liu P, Zhang X (2022) The double-edged sword of SIRT3 in cancer and its therapeutic applications. Front Pharmacol 13:871560. https://doi.org/10.3389/fphar.2022.871560 PubMed DOI PMC

Parascandolo A, Laukkanen MO (2019) Carcinogenesis and reactive oxygen species signaling: interaction of the NADPH oxidase NOX1-5 and superoxide dismutase 1–3 signal transduction pathways. Antioxid Redox Signal 30(3):443–486. https://doi.org/10.1089/ars.2017.7268 PubMed DOI PMC

Park Y, Spiegelman D, Hunter DJ et al (2010) Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies. Cancer Causes Control 21(11):1745–1757. https://doi.org/10.1007/s10552-010-9549-y PubMed DOI PMC

Pei X, Xiao J, Wei G, Zhang Y (2019) Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway. Chem Biol Interact 298:112–120. https://doi.org/10.1016/j.cbi.2018.09.021 PubMed DOI

Pei J, Pan X, Wei G, Hua Y (2023) Research progress of glutathione peroxidase family (GPX) in redoxidation. Front Pharmacol 14:1147414. https://doi.org/10.3389/fphar.2023.1147414 PubMed DOI PMC

Peña-Blanco A, García-Sáez AJ (2018) Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J 285(3):416–431. https://doi.org/10.1111/febs.14186 PubMed DOI

Perillo B, Di Donato M, Pezone A et al (2020) ROS in cancer therapy: the bright side of the moon. Exp Mol Med 52:192–203. https://doi.org/10.1038/s12276-020-0384-2 PubMed DOI PMC

Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8(1):49–62. https://doi.org/10.1038/nrm2083 PubMed DOI

Perkins ND (2012) The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer 12(2):121–132. https://doi.org/10.1038/nrc3204 PubMed DOI

Perry JJ, Shin DS, Getzoff ED et al (2010) The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta 1804(2):245–262. https://doi.org/10.1016/j.bbapap.2009.11.004 PubMed DOI

Pervaiz S, Chong SJF (2018) Rac1-induced ROS is implicated in the sustained activation of anti-apoptotic protein Bcl-2 in cancer cells. Free Radic Biol Med 128(suppl):S71. https://doi.org/10.1016/j.freeradbiomed.2018.10.155 DOI

Piskounova E, Agathocleous M, Murphy MM et al (2015) Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 527(7577):186–191. https://doi.org/10.1038/nature15726 PubMed DOI PMC

Plymate SR, Haugk KH, Sprenger CC, Nelson PS et al (2003) Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1. Oncogene 22(7):1024–1034. https://doi.org/10.1038/sj.onc.1206210 PubMed DOI

Podmore I, Griffiths H, Herbert K et al (1998) Vitamin C exhibits pro-oxidant properties. Nature 392:559. https://doi.org/10.1038/33308 PubMed DOI

Ponsero AJ, Igbaria A, Darch MA, Miled S et al (2017) Endoplasmic reticulum transport of glutathione by Sec61 Is regulated by Ero1 and Bip. Mol Cell 67(6):962-973.e5. https://doi.org/10.1016/j.molcel.2017.08.012 PubMed DOI PMC

Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M (2017) Targeting free radicals in oxidative stress-related human diseases. Trends Pharmacol Sci 38(7):592–607. https://doi.org/10.1016/j.tips.2017.04.005 PubMed DOI

Powers SK, Ji LL, Kavazis AN, Jackson MJ (2011) Reactive oxygen species: impact on skeletal muscle. Compr Physiol 1(2):941–969. https://doi.org/10.1002/cphy.c100054 PubMed DOI PMC

Prajapati P, Sripada L, Singh K, Bhatelia K et al (2015) TNF-α regulates miRNA targeting mitochondrial complex-I and induces cell death in dopaminergic cells. Biochim Biophys Acta 1852(3):451–461. https://doi.org/10.1016/j.bbadis.2014.11.019 PubMed DOI

Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9:285–293. https://doi.org/10.1038/nrc2621 PubMed DOI PMC

Punganuru SR, Madala HR, Arutla V, Srivenugopal KS (2018) Selective killing of human breast cancer cells by the styryl lactone (R)-goniothalamin is mediated by glutathione conjugation, induction of oxidative stress and marked reactivation of the R175H mutant p53 protein. Carcinogenesis 39(11):1399–1410. https://doi.org/10.1093/carcin/bgy093 PubMed DOI

Raaschou-Nielsen O, Sørensen M, Hansen RD, Frederiksen K et al (2007) GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption, and risk for lung cancer. Cancer Lett 247:293–300. https://doi.org/10.1016/j.canlet.2006.05.006 PubMed DOI

Radisky D, Levy D, Littlepage L et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127. https://doi.org/10.1038/nature03688 PubMed DOI PMC

Raimondi V, Ciccarese F, Ciminale V (2020) Oncogenic pathways and the electron transport chain: a dange ROS liaison. Br J Cancer 122(2):168–181. https://doi.org/10.1038/s41416-019-0651-y PubMed DOI

Rainis T, Maor I, Lanir A, Shnizer S, Lavy A (2007) Enhanced oxidative stress and leucocyte activation in neoplastic tissues of the colon. Dig Dis Sci 52:526–530. https://doi.org/10.1007/s10620-006-9177-2 PubMed DOI

Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K et al (2001) Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A 98(6):3410–3415. https://doi.org/10.1073/pnas.051618798 PubMed DOI PMC

Reczek CR, Chandel NS (2017) The two faces of reactive oxygen species in cancer. Ann Rev Cancer Biol 1:79–98. https://doi.org/10.1146/annurev-cancerbio-041916-065808 DOI

Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 12:2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012 DOI

Ren Z, Liang H, Galbo PM Jr, Dharmaratne M et al (2022) Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer. Proc Natl Acad Sci USA 119(8):e2107266119. https://doi.org/10.1073/pnas.2107266119 PubMed DOI PMC

Rodrigues P, Vanharanta S (2019) Circulating tumor cells: come together, right now. Over Metastasis Cancer Discov 9(1):22–24. https://doi.org/10.1158/2159-8290.CD-18-1285 PubMed DOI

Romagnolo DF, Selmin OI (2012) Flavonoids and cancer prevention: a review of the evidence. J Nutr Gerontol Geriatr 31(3):206–238. https://doi.org/10.1080/21551197.2012.702534 PubMed DOI

Romero R, Sayin VI, Davidson SM et al (2017) Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med 23(11):1362–1368. https://doi.org/10.1038/nm.440 PubMed DOI PMC

Rose Li Y, Halliwill KD, Adams CJ (2020) Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice. Nat Commun 11(1):394. https://doi.org/10.1038/s41467-019-14261-4 PubMed DOI PMC

Rusolo F, Capone F, Pasquale R, Angiolillo A et al (2017) Comparison of the seleno-transcriptome expression between human non-cancerous mammary epithelial cells and two human breast cancer cell lines. Oncol Lett 13(4):2411–2417. https://doi.org/10.3892/ol.2017.5715 PubMed DOI PMC

Sage E, Harrison L (2011) Clustered DNA lesion repair in eukaryotes: relevance to mutagenesis and cell survival. Mutat Res 711(1–2):123–133. https://doi.org/10.1016/j.mrfmmm.2010.12.010 PubMed DOI

Saitoh M, Nishitoh H, Fujii M, Takeda K (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17(9):2596–2606. https://doi.org/10.1093/emboj/17.9.2596 PubMed DOI PMC

Samoylenko A, Hossain JA, Mennerich D, Kellokumpu S, Hiltunen JK, Kietzmann T (2013) Nutritional countermeasures targeting reactive oxygen species in cancer: from mechanisms to biomarkers and clinical evidence. Antioxid Redox Signal 19(17):2157–2196. https://doi.org/10.1089/ars.2012.4662 PubMed DOI PMC

Sander CS, Hamm F, Elsner P, Thiele JJ (2003) Oxidative stress in malignant melanoma and non-melanoma skin cancer. Br J Dermatol 148:913–922. https://doi.org/10.1046/j.1365-2133.2003.05303.x PubMed DOI

Sarmiento-Salinas FL, Perez-Gonzalez A, Acosta-Casique A, Ix-Ballote A et al (2021) Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression. Life Sci 284:119942. https://doi.org/10.1016/j.lfs.2021.119942 PubMed DOI

Satooka H, Hara-Chikuma M (2016) Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling. Mol Cell Biol 36(7):1206–1218. https://doi.org/10.1128/MCB.00971-15 PubMed DOI PMC

Sayin VI, Ibrahim MX, Larsson E, Nilsson JA et al (2014) Antioxidants accelerate lung cancer progression in mice. Sci Transl Med 6(221):221ra15. https://doi.org/10.1126/scitranslmed.3007653 PubMed DOI

Schafer ZT, Grassian AR, Song L, Jiang Z et al (2009) Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461(7260):109–113. https://doi.org/10.1038/nature08268 PubMed DOI PMC

Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399–408. https://doi.org/10.1016/j.cell.2012.01.021 PubMed DOI PMC

Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL et al (2009) Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138(1):90–103. https://doi.org/10.1016/j.cell.2009.06.021 PubMed DOI PMC

Shadel GS, Horvath TL (2015) Mitochondrial ROS signaling in organismal homeostasis. Cell 163(3):560–569. https://doi.org/10.1016/j.cell.2015.10.001 PubMed DOI PMC

Shafirovich V, Geacintov NE (2017) Removal of oxidatively generated DNA damage by overlapping repair pathways. Free Radic Biol Med 107:53–61. https://doi.org/10.1016/j.freeradbiomed.2016.10.507 PubMed DOI

Shao J, Li M, Guo Z et al (2019) TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1. Cell Commun Signal 17:149. https://doi.org/10.1186/s12964-019-0468-6 PubMed DOI PMC

Shi T, Dansen TB (2020a) Reactive oxygen species induced p53 activation: DNA damage, redox signaling, or both? Antioxid Redox Signal 33(12):839–859. https://doi.org/10.1089/ars.2020.8074 PubMed DOI

Shi T, Dansen TB (2020b) ROS induced p53 activation: DNA damage, redox signaling or both? Antioxid Redox Signal. https://doi.org/10.1089/ars.2020.8074] PubMed DOI PMC

Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics. CA Cancer J Clin 74(1):12–49. https://doi.org/10.3322/caac.21820 PubMed DOI

Sies H (2017) Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Redox Biol 11:613–619. https://doi.org/10.1016/j.redox.2016.12.035 PubMed DOI PMC

Sies H (2019) Oxidative stress: eustress and distress in redox homeostasis. In: Fink G (ed) Stress: physiology, biochemistry, and pathology handbook of stress series. Academic Press, Elsevier, pp 153–163. https://doi.org/10.1016/B978-0-12-813146-6.00013-8 DOI

Sies H (2023) Oxidative eustress: the physiological role of oxidants. Sci China Life Sci 66(8):1947–1948. https://doi.org/10.1007/s11427-023-2336-1 PubMed DOI

Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 21(7):363–383. https://doi.org/10.1038/s41580-020-0230-3 PubMed DOI

Simunkova M, Alwasel SH, Alhazza IM, Jomova K, Kollar V, Rusko M, Valko M (2019) Management of oxidative stress and other pathologies in Alzheimer’s disease. Arch Toxicol 93(9):2491–2513. https://doi.org/10.1007/s00204-019-02538-y PubMed DOI

Simunkova M, Barbierikova Z, Jomova K, Hudecova L, Lauro P, Alwasel SH, Alhazza I, Rhodes CJ, Valko M (2021) Antioxidant vs. prooxidant properties of the flavonoid, kaempferol, in the presence of Cu(II) Ions: a ROS-scavenging activity, fenton reaction and DNA damage study. Int J Mol Sci 22(4):1619. https://doi.org/10.3390/ijms22041619 PubMed DOI PMC

Siska PJ, Beckermann KE, Mason FM et al (2017) Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. JCI Insight 2(12):e93411. https://doi.org/10.1172/jci.insight.93411 PubMed DOI PMC

Slatore CG, Littman AJ, Au DH, Satia JA, White E (2008) Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med 177(5):524–530. https://doi.org/10.1164/rccm.200709-1398OC PubMed DOI

Son J, Lyssiotis C, Ying H et al (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496:101–105. https://doi.org/10.1038/nature12040 PubMed DOI PMC

Stanley LA (2017). Drug metabolism, Pharmacognosy: Fundamentals, Applications and Strategies, pp 527–545. https://doi.org/10.1016/B978-0-12-802104-0.00027-5

Su X, Shen Z, Yang Q, Sui F et al (2019) Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics 9(15):4461–4473. https://doi.org/10.7150/thno.35219 PubMed DOI PMC

Sugezawa K, Morimoto M, Yamamoto M et al (2022) GPX4 regulates tumor cell proliferation via suppressing ferroptosis and exhibits prognostic significance in gastric cancer. Anticancer Res 42(12):5719–5729. https://doi.org/10.21873/anticanres.16079 PubMed DOI

Szabo PM, Vajdi A, Kumar N et al (2023) Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment. Sci Rep 13:3051. https://doi.org/10.1038/s41598-023-28480-9 PubMed DOI PMC

Sznarkowska A, Kostecka A, Meller K, Bielawski K (2017) Inhibition of cancer antioxidant defense by natural compounds. Oncotarget 8:15996–16016. https://doi.org/10.18632/oncotarget.13723 PubMed DOI

Takahashi N, Chen HY, Harris IS, Stover DG et al (2018) Cancer cells co-opt the neuronal redox-sensing channel TRPA1 to promote oxidative-stress tolerance. Cancer Cell 33(6):985-1003.e7. https://doi.org/10.1016/j.ccell.2018.05.001 PubMed DOI PMC

Tanaka A, Node K (2022) Xanthine oxidase inhibition for cardiovascular disease prevention. Lancet 400(10359):1172–1173. https://doi.org/10.1016/S0140-6736(22)01778-0 PubMed DOI

Taniguchi K, Karin M (2018) NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 18(5):309–324. https://doi.org/10.1038/nri.2017.142 PubMed DOI

Tasdogan A, Faubert B, Ramesh V, Ubellacker JM et al (2020) Metabolic heterogeneity confers differences in melanoma metastatic potential. Nature 577(7788):115–120. https://doi.org/10.1038/s41586-019-1847-2 PubMed DOI

Tasdogan A, Ubellacker JM, Morrison SJ (2021) Redox regulation in cancer cells during metastasis. Cancer Discov 11(11):2682–2692. https://doi.org/10.1158/2159-8290.CD-21-0558 PubMed DOI PMC

Taylor CT, Scholz CC (2022) The effect of HIF on metabolism and immunity. Nat Rev Nephrol 18:573–587. https://doi.org/10.1038/s41581-022-00587-8 PubMed DOI PMC

Taylor A, Robson A, Houghton BC, Jepson CA et al (2013) Epididymal specific, selenium-independent GPX5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation. Hum Reprod 28(9):2332–2342. https://doi.org/10.1093/humrep/det237 PubMed DOI

Terao J (2023) Revisiting carotenoids as dietary antioxidants for human health and disease prevention. Food Funct 14(17):7799–7824. https://doi.org/10.1039/d3fo02330c PubMed DOI

Thamilselvan V, Menon M, Stein GS, Valeriote F, Thamilselvan S (2017) Combination of carmustine and selenite inhibits EGFR mediated growth signaling in androgen-independent prostate cancer cells. J Cell Biochem 118(12):4331–4340. https://doi.org/10.1002/jcb.26086 PubMed DOI

Timoshnikov VA, Kobzeva TV, Polyakov NE, Kontoghiorghes GJ (2020) Redox interactions of vitamin C and iron: inhibition of the pro-oxidant activity by deferiprone. Int J Mol Sci 21(11):3967. https://doi.org/10.3390/ijms21113967 PubMed DOI PMC

Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K et al (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2:222–228. https://doi.org/10.1093/embo-reports/kve046 PubMed DOI PMC

Torrens-Mas M, Oliver J, Roca P, Sastre-Serra J (2017) SIRT3: oncogene and tumor suppressor in cancer. Cancers (Basel) 9:90. https://doi.org/10.3390/cancers9070090 PubMed DOI

Torti SV, Manz DH, Paul BT, Blanchette-Farra N, Torti FM (2018) Iron and Cancer. Annu Rev Nutr 38:97–125. https://doi.org/10.1146/annurev-nutr-082117-051732 PubMed DOI PMC

Tsugane S, Sasazuki S (2007) Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer 10(2):75–83. https://doi.org/10.1007/s10120-007-0420-0 PubMed DOI

Tubbs A, Nussenzweig A (2017) Endogenous DNA damage as a source of genomic instability in cancer. Cell 168(4):644–656. https://doi.org/10.1016/j.cell.2017.01.002 PubMed DOI PMC

Ubellacker JM, Tasdogan A, Ramesh V (2020) Lymph protects metastasizing melanoma cells from ferroptosis. Nature 585(7823):113–118. https://doi.org/10.1038/s41586-020-2623-z PubMed DOI PMC

Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C (1982) Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim Biophys Acta 710(2):197–211. https://doi.org/10.1016/0005-2760(82)90150-3 PubMed DOI

Valavanidis A, Vlachogianni T, Fiotakis C (2009) 8-hydroxy-2′ -deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C 27(2):120–139. https://doi.org/10.1080/10590500902885684 DOI

Valko M, Jomova K, Rhodes CJ, Kuča K, Musílek K (2016) Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol 90(1):1–37. https://doi.org/10.1007/s00204-015-1579-5 PubMed DOI

Van Remmen H, Ikeno Y, Hamilton M et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16(1):29–37. https://doi.org/10.1152/physiolgenomics.00122.2003 PubMed DOI

Veeramachaneni S, Wang XD (2009) Carotenoids and lung cancer prevention. Front Biosci (Schol Ed) 1(1):258–274. https://doi.org/10.2741/S25 PubMed DOI

Veith A, Moorthy B (2018) Role of cytochrome P450S in the generation and metabolism of reactive oxygen species. Curr Opin Toxicol 7:44–51. https://doi.org/10.1016/j.cotox.2017.10.003 PubMed DOI

Verma IM, Ransone LJ, Visvader J, Sassone-Corsi P, Lamph WW (1990) fos-jun conspiracy: implications for the cell. Ciba Found Symp 150:128–137. https://doi.org/10.1002/9780470513927.ch9 PubMed DOI

Virtamo J, Taylor PR, Kontto J, Männistö S et al (2014) Effects of α-tocopherol and β-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the alpha-tocopherol, beta-carotene cancer prevention study. Int J Cancer 135(1):178–185. https://doi.org/10.1002/ijc.28641 PubMed DOI

Viswanathan VS, Ryan MJ, Dhruv HD et al (2017) Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547(7664):453–457. https://doi.org/10.1038/nature23007 PubMed DOI PMC

Vlasveld LT, Janssen R, Bardou-Jacquet E, Venselaar H, Hamdi-Roze H, Drakesmith H, Swinkels DW (2019) Twenty years of ferroportin disease: a review or an update of published clinical, biochemical, molecular, and functional features. Pharmaceuticals (Basel) 12(3):132. https://doi.org/10.3390/ph12030132 PubMed DOI

Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9(8):537–549. https://doi.org/10.1038/nrc2694 PubMed DOI

Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, Kang MI, Kobayashi A, Yamamoto M, Kensler TW, Talalay P (2004) Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci U S A 101(7):2040–2045. https://doi.org/10.1073/pnas.0307301101 PubMed DOI PMC

Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92(12):5510–5514. https://doi.org/10.1073/pnas.92.12.5510 PubMed DOI PMC

Wang Y, Cui R, Xiao Y, Fang J, Xu Q (2015) Effect of carotene and lycopene on the risk of prostate cancer: a systematic review and dose-response meta-analysis of observational studies. PLoS ONE 10(9):e0137427. https://doi.org/10.1371/journal.pone.0137427 PubMed DOI PMC

Wang Y, Branicky R, Noë A, Hekimi S (2018) Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol 217(6):1915–1928. https://doi.org/10.1083/jcb.201708007 PubMed DOI PMC

Wang J, Deng H, Zhang J, Wu D, Li J, Ma J, Dong W (2020) α-Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway. Phytother Res 34(3):601–611. https://doi.org/10.1002/ptr.6548 PubMed DOI

Wang Y, Yen FS, Zhu XG, Timson RC et al (2021) SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. Nature 599(7883):136–140. https://doi.org/10.1038/s41586-021-04025-w PubMed DOI PMC

Wang Y, Kuca K, You L, Nepovimova E, Heger Z, Valko M, Adam V, Wu Q, Jomova K (2024) The role of cellular senescence in neurodegenerative diseases. Arch Toxicol 98(8):2393–2408. https://doi.org/10.1007/s00204-024-03768-5 PubMed DOI PMC

Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8(6):519–530. https://doi.org/10.1085/jgp.8.6.519 PubMed DOI PMC

Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3):225–234. https://doi.org/10.1016/j.ccr.2010.01.020 PubMed DOI PMC

Waypa GB, Schumacker PT (2008) Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age-old question. Exp Physiol 93(1):133–138. https://doi.org/10.1113/expphysiol.2007.041236 PubMed DOI

Wei R, Qiu H, Xu J, Mo J et al (2020) Expression and prognostic potential of GPX1 in human cancers based on data mining. Ann Transl Med 8(4):124. https://doi.org/10.21037/atm.2020.02.36 PubMed DOI PMC

Wei S, Yu Z, Shi R et al (2022) GPX4 suppresses ferroptosis to promote malignant progression of endometrial carcinoma via transcriptional activation by ELK1. BMC Cancer 22:881. https://doi.org/10.1186/s12885-022-09986-3 PubMed DOI PMC

White K, Someya S (2023) The roles of NADPH and isocitrate dehydrogenase in cochlear mitochondrial antioxidant defense and aging. Hear Res 427:108659. https://doi.org/10.1016/j.heares.2022.108659 PubMed DOI

Wiel C, Le Gal K, Ibrahim MX, Jahangir CA et al (2019) BACH1 stabilization by antioxidants stimulates lung cancer metastasis. Cell 178(2):330-345.e22. https://doi.org/10.1016/j.cell.2019.06.005 PubMed DOI

Wishart DS (2015) Is cancer a genetic disease or a metabolic disease? EBioMedicine 2(6):478–479. https://doi.org/10.1016/j.ebiom.2015.05.022 PubMed DOI PMC

Woo HD, Kim J (2013) Dietary flavonoid intake and smoking-related cancer risk: a meta-analysis. PLoS ONE 8(9):e75604. https://doi.org/10.1371/journal.pone.0075604 PubMed DOI PMC

Wu Q, Ni X (2015) ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr Drug Targets 16(1):13–19. https://doi.org/10.2174/1389450116666150113121054 PubMed DOI

Xia Y, Shen S, Verma IM (2014) NF-κB, an active player in human cancers. Cancer Immunol Res 2(9):823–830. https://doi.org/10.1158/2326-6066 PubMed DOI PMC

Xiao GG, Wang M, Li N, Loo JA, Nel AE (2003) Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem 278(50):50781–50790. https://doi.org/10.1074/jbc.M306423200 PubMed DOI

Xiong Y, Wang M, Zhao J, Han Y, Jia L (2016) Sirtuin 3: a Janus face in cancer (review). Int J Oncol 49:2227–2235. https://doi.org/10.3892/ijo.2016.3767 PubMed DOI

Yamane T, Nakatani H, Kikuoka N, Matsumoto H et al (1996) Inhibitory effects and toxicity of green tea polyphenols for gastrointestinal carcinogenesis. Cancer 77(8 Suppl):1662–1667. https://doi.org/10.1002/(SICI)1097-0142(19960415)77:8%3c1662::AID-CNCR36%3e3.0.CO;2-W PubMed DOI

Yang Y, Cao Y (2022) The impact of VEGF on cancer metastasis and systemic disease. Semin Cancer Biol 86(Pt 3):251–261. https://doi.org/10.1016/j.semcancer.2022.03.011 PubMed DOI

Yang CS, Yang GY, Landau JM, Kim S, Liao J (1998) Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and tumor progression. Exp Lung Res 24(4):629–639. https://doi.org/10.3109/01902149809087391 PubMed DOI

Yang Y, Dieter MZ, Chen Y, Shertzer HG, Nebert DW, Dalton TP (2002) Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm (-/-) knockout mouse. novel model system for a severely compromised oxidative stress response. J Biol Chem 277(51):49446–49452. https://doi.org/10.1074/jbc.M209372200 PubMed DOI

Yang M, Zhu X, Shen Y, He Q et al (2022) GPX2 predicts recurrence-free survival and triggers the Wnt/β-catenin/EMT pathway in prostate cancer. PeerJ 10:e14263. https://doi.org/10.7717/peerj.14263 PubMed DOI PMC

Yang Y, Huang G, Lian J, Long C (2024) Circulating tumour cell clusters: isolation, biological significance and therapeutic implications. BMJ Oncol 3(1):e000437. https://doi.org/10.1136/bmjonc-2024-000437 PubMed DOI PMC

Yano S, Yano N (2002) Regulation of catalase enzyme activity by cell signaling molecules. Mol Cell Biochem 240:119–130. https://doi.org/10.1023/A:1020680131754 PubMed DOI

Yao J, Chen X, Liu Z, Zhang R et al (2021) The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients. Chin Neurosurg J 7(1):21. https://doi.org/10.1186/s41016-021-00235-3 PubMed DOI PMC

Ye X, Weinberg RA (2015) Epithelial-mesenchymal plasticity: a central regulator of cancer progression. Trends Cell Biol 25(11):675–686. https://doi.org/10.1016/j.tcb.2015.07.012 PubMed DOI PMC

Yi Z, Jiang L, Zhao L, Zhou M, Ni Y et al (2019) Glutathione peroxidase 3 (GPX3) suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of hypoxia-inducible factor 1-α and 2-α. J Cell Biochem 120:19124–19136. https://doi.org/10.1002/jcb.29240 PubMed DOI

Yu B, Liu Y, Peng X, Hua S, Zhou G, Yan K, Liu Y (2020) Synthesis, characterization, and antitumor properties of Au(i)-thiourea complexes. Metallomics 12(1):104–113. https://doi.org/10.1039/c9mt00232d PubMed DOI

Yuan Z, Liang Z, Yi J, Chen X, Li R, Wu J, Sun Z (2019) Koumine promotes ROS production to suppress hepatocellular carcinoma cell proliferation via NF-κB and ERK/p38 MAPK signaling. Biomolecules 9(10):559. https://doi.org/10.3390/biom9100559 PubMed DOI PMC

Yun Y, Gao R, Yue H, Guo L, Li G, Sang N (2017) Sulfate aerosols promote lung cancer metastasis by epigenetically regulating the epithelial-to-mesenchymal transition (EMT). Environ Sci Technol 51(19):11401–11411. https://doi.org/10.1021/acs.est.7b02857 PubMed DOI

Zhang XY, Hong SS, Zhang M, Cai QQ, Zhang MX, Xu CJ (2018) Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets. Neoplasma 65(1):104–112. https://doi.org/10.4149/neo_2018_101 PubMed DOI

Zhang X, Xu H, Zhang Y, Sun C et al (2022) Immunohistochemistry and bioinformatics identify GPX8 as a potential prognostic biomarker and target in human gastric cancer. Front Oncol 12:878546. https://doi.org/10.3389/fonc.2022.878546 PubMed DOI PMC

Zhang W, Liu Y, Liao Y, Zhu C, Zou Z (2024) GPX4, ferroptosis, and diseases. Biomed Pharmacother 174:116512. https://doi.org/10.1016/j.biopha.2024.116512 PubMed DOI

Zhao RZ, Jiang S, Zhang L, Yu ZB (2019) Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med 44(1):3–15. https://doi.org/10.3892/ijmm.2019.4188 PubMed DOI PMC

Zhao S, Allis CD, Wang GG (2021) The language of chromatin modification in human cancers. Nat Rev Cancer 21(7):413–430. https://doi.org/10.1038/s41568-021-00357-x PubMed DOI PMC

Zhao Y, Wang H, Zhou J, Shao Q (2022) Glutathione peroxidase GPX1 and its dichotomous roles in cancer. Cancers 14(10):2560. https://doi.org/10.3390/cancers14102560 PubMed DOI PMC

Zheng Y, Miyamoto D, Wittner B et al (2017) Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination. Nat Commun 8:14344. https://doi.org/10.1038/ncomms14344 PubMed DOI PMC

Zhou Q, Meng Y, Li D et al (2024) Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies. Sig Transduct Target Ther 9:55. https://doi.org/10.1038/s41392-024-01769-5 DOI