Roles of reactive oxygen species in inflammation and cancer

Yunfei Yu, Shengzhuo Liu, Luchen Yang, Pan Song, Zhenghuan Liu, Xiaoyang Liu, Xin Yan, Qiang Dong()

PDF
MedComm ›› 2024, Vol. 5 ›› Issue (4) : e519. DOI: 10.1002/mco2.519
REVIEW

Roles of reactive oxygen species in inflammation and cancer

  • Yunfei Yu, Shengzhuo Liu, Luchen Yang, Pan Song, Zhenghuan Liu, Xiaoyang Liu, Xin Yan, Qiang Dong()
Author information +
History +

Abstract

Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.

Keywords

cancer / immune / reactive oxygen species / treatment

Cite this article

Download citation ▾
Yunfei Yu, Shengzhuo Liu, Luchen Yang, Pan Song, Zhenghuan Liu, Xiaoyang Liu, Xin Yan, Qiang Dong. Roles of reactive oxygen species in inflammation and cancer. MedComm, 2024, 5(4): e519 https://doi.org/10.1002/mco2.519

References

1 H Sies, DP Jones. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7): 363-383.
2 B D'Autréaux, MB Toledano. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol. 2007; 8(10): 813-824.
3 M Deponte. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta. 2013; 1830: 3217-3266.
4 J Nordberg, ES Arnér. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med. 2001; 31: 1287-1312.
5 MG Netea, F Balkwill, M Chonchol, et al. A guiding map for inflammation. Nat, Immunol. 2017; 18(8): 826-831.
6 FR Greten, SI Grivennikov. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity. 2019; 51: 27-41.
7 M Marozzi, A Parnigoni, A Negri, et al. Inflammation, extracellular matrix remodeling, and proteostasis in tumor microenvironment. Int J Mol Sci. 2021; 22(15): 8102. doi:
8 P Silwal, JK Kim, YJ Kim, EK Jo. Mitochondrial reactive oxygen species: double-edged weapon in host defense and pathological inflammation during infection. Front Immunol. 2020; 11: 1649.
9 S Saikolappan, B Kumar, G Shishodia, S Koul, HK Koul. Reactive oxygen species and cancer: a complex interaction. Cancer Lett. 2019; 452: 132-143.
10 V Aggarwal, HS Tuli, A Varol, et al. Role of reactive oxygen species in cancer progression: molecular mechanisms and recent advancements. Biomolecules. 2019; 9(11): 735. doi:
11 EC Rosenow, FH Johnson. Studies on the nature of antibodies produced in vitro from bacteria with hydrogen peroxide and heat. J Bacteriol. 1946; 55(3): 219-232.
12 JA Badwey, ML Karnovsky. Active oxygen species and the functions of phagocytic leukocytes. Annu Rev Biochem. 1980; 49: 695-726.
13 H Carp, A Janoff. In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes. J Clin Invest. 1979; 63(4): 793-797.
14 SA Weitzman, LI Gordon. Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood. 1990; 76: 655-663.
15 AP West, IE Brodsky, C Rahner, et al. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature. 2011; 472(7344): 476-480.
16 SJ Dixon, KM Lemberg, MR Lamprecht, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012; 149: 1060-1072.
17 W Wang, M Green, JE Choi, et al. CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019; 569: 270-274.
18 R Kim, A Hashimoto, N Markosyan, et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature. 2022; 612: 338-346.
19 AA Starkov. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci. 2008; 1147: 37-52.
20 X Li, P Fang, J Mai, ET Choi, H Wang, XF Yang. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013; 6: 19.
21 H Sch?gger, K Pfeiffer. The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J Biol Chem. 2001; 276: 37861-37867.
22 BM Babior, JD Lambeth, W Nauseef. The neutrophil NADPH oxidase. Arch Biochem Biophys. 2002; 397: 342-344.
23 M Ushio-Fukai. Localizing NADPH oxidase-derived ROS. Sci STKE. 2006; 2006: re8.
24 P Storz. Reactive oxygen species in tumor progression. Front Biosci. 2005; 10: 1881-1896.
25 D Beyersmann, A Hartwig. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol. 2008; 82(8): 493-512.
26 LM Bystrom, ML Guzman, S Rivella. Iron and reactive oxygen species: friends or foes of cancer cells? Antioxid Redox Signal. 2014; 20: 1917-1924.
27 EA Veal, AM Day, BA Morgan. Hydrogen peroxide sensing and signaling. Mol Cell. 2007; 26: 1-14.
28 C Nathan, A Ding. SnapShot: reactive oxygen intermediates (ROI). Cell. 2010; 140: 951-951. e2.
29 G Hughes, MP Murphy, EC Ledgerwood. Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor kappaB to modulate tumour necrosis factor-induced apoptosis: evidence from mitochondria-targeted antioxidants. Biochem J. 2005; 389: 83-89.
30 A Corcoran, TG Cotter. Redox regulation of protein kinases. FEBS J. 2013; 280: 1944-1965.
31 S Win, TA Than, JC Fernandez-Checa, N Kaplowitz. JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death. Cell Death Dis. 2014; 5:e989.
32 J Li, X Hu, P Selvakumar, et al. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab. 2004; 287: E834-E841.
33 F Esposito, G Chirico, N Montesano Gesualdi, et al. Protein kinase B activation by reactive oxygen species is independent of tyrosine kinase receptor phosphorylation and requires SRC activity. J Biol Chem. 2003; 278(23): 20828-20834.
34 M Sundaresan, ZX Yu, VJ Ferrans, K Irani, T Finkel. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995; 270: 296-299.
35 GL Wang, BH Jiang, EA Rue, GL Semenza. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995; 92(12): 5510-5514.
36 I Martínez-Reyes, LP Diebold, H Kong, et al. TCA cycle and mitochondrial membrane potential are necessary for diverse biological functions. Mol Cell. 2016; 61: 199-209.
37 CW Pugh, PJ Ratcliffe. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003; 9: 677-684.
38 F De Smet, I Segura, K De Bock, PJ Hohensinner, P Carmeliet. Mechanisms of vessel branching: filopodia on endothelial tip cells lead the way. Arterioscler Thromb Vasc Biol. 2009; 29: 639-649.
39 N Ferrara. VEGF-A: a critical regulator of blood vessel growth. Eur Cytokine Netw. 2009; 20: 158-163.
40 A Hoeben, B Landuyt, MS Highley, H Wildiers, AT Van Oosterom, EA De Bruijn. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56: 549-580.
41 DD Roberts. Extracellular matrix and redox signaling in cellular responses to stress. Antioxid Redox Signal. 2017; 27: 771-773.
42 CK Sen, S Roy. Redox signals in wound healing. Biochim Biophys Acta. 2008; 1780: 1348-1361.
43 B Singla, R Holmdahl, G Csanyi. Editorial: oxidants and redox signaling in inflammation. Front Immunol. 2019; 10: 545.
44 R Janke, AE Dodson, J Rine. Metabolism and epigenetics. Annu Rev Cell Dev Biol. 2015; 31: 473-496.
45 E Mosharov, MR Cranford, R Banerjee. The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes. Biochemistry. 2000; 39(42): 13005-13011.
46 I Martínez-Reyes, NS Chandel. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020; 11: 102.
47 L Tretter, V Adam-Vizi. Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci. 2000; 20: 8972-8979.
48 Y Tsuchiya, SY Peak-Chew, C Newell, et al. Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. Biochem J. 2017; 474: 2489-2508.
49 C Vicente-Gutierrez, N Bonora, V Bobo-Jimenez, et al. Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour. Nat Metab. 2019; 1: 201-211.
50 M Jaud, C Philippe, D Di Bella, et al. Translational regulations in response to endoplasmic reticulum stress in cancers. Cells. 2020; 9(3): 540. doi:
51 CM Grant. Regulation of translation by hydrogen peroxide. Antioxid Redox Signal. 2011; 15: 191-203.
52 T Adomavicius, M Guaita, Y Zhou, et al. The structural basis of translational control by eIF2 phosphorylation. Nat Commun. 2019; 10: 2136.
53 L Galluzzi, I Vitale, JM Abrams, et al. Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ. 2012; 19: 107-120.
54 JM Heo, N Livnat-Levanon, EB Taylor, et al. A stress-responsive system for mitochondrial protein degradation. Mol Cell. 2010; 40: 465-480.
55 RJ Braun, H Zischka, F Madeo, et al. Crucial mitochondrial impairment upon CDC48 mutation in apoptotic yeast. J Biol Chem. 2006; 281(35): 25757-25767.
56 VE Kagan, VA Tyurin, J Jiang, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol. 2005; 1(4): 223-232.
57 Y Yang, E White. Autophagy suppresses TRP53/p53 and oxidative stress to enable mammalian survival. Autophagy. 2020; 16: 1355-1357.
58 X Guo, S Hong, H He, et al. NFκB promotes oxidative stress-induced necrosis and ischemia/reperfusion injury by inhibiting Nrf2-ARE pathway. Free Radic Biol Med. 2020; 159: 125-135.
59 X Jiang, B Stockwell, M Conrad. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021; 22: 266-282.
60 Y Liu, W Gu. p53 in ferroptosis regulation: the new weapon for the old guardian. Cell Death Differ. 2022; 29: 895-910.
61 G Liu, X Chen. The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis. Oncogene. 2002; 21(47): 7195-7204.
62 L Jiang, N Kon, T Li, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015; 520(7545): 57-62.
63 T Humpton, H Hall, C Kiourtis, et al. p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl(4). Cell Death Differ. 2022; 29: 514-526.
64 JM DeBlasi, G DeNicola. Dissecting the crosstalk between NRF2 signaling and metabolic processes in cancer. Cancers. 2020;12(10):3023. doi:
65 GX Semenza. Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype. EMBO J. 2017;36:252-259.
66 G Lee, HS Won, YM Lee, et al. Oxidative dimerization of PHD2 is responsible for its inactivation and contributes to metabolic reprogramming via HIF-1α activation. Sci Rep. 2016;6:18928.
67 GJ Kops, TB Dansen, PE Polderman, et al. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature. 2002;419:316-321.
68 S Nemoto, T Finkel. Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science. 2002;295(5564):2450-2452.
69 Y Zhao, Y Wang, WG Zhu. Applications of post-translational modifications of FoxO family proteins in biological functions. J Mol Cell Biol. 2011;3:276-282.
70 J Sun, H Hoshino, K Takaku, et al. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. EMBO J. 2002;21:5216-5224.
71 HJ Warnatz, D Schmidt, T Manke, et al. The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle. J Biol Chem. 2011;286:23521-23532.
72 C Wiel, K Le Gal, MX Ibrahim, et al. BACH1 stabilization by antioxidants stimulates lung cancer metastasis. Cell. 2019;178:330-345. e22.
73 M Yamamoto, TW Kensler, H Motohashi. The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev. 2018;98:1169-1203.
74 TT Zhang, N Qu, GH Sun, et al. NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer. Int J Oncol. 2018;53:685-693.
75 SE Eriksson, S Ceder, VJN Bykov, KG Wiman. p53 as a hub in cellular redox regulation and therapeutic target in cancer. J Mol Cell Biol. 2019;11(4):330-341.
76 A Ferino, V Rapozzi, LE Xodo. The ROS-KRAS-Nrf2 axis in the control of the redox homeostasis and the intersection with survival-apoptosis pathways: implications for photodynamic therapy. J Photochem Photobiol B. 2020;202:111672.
77 Z Qiang, H Dong, Y Xia, D Chai, R Hu, H Jiang. Nrf2 and STAT3 alleviates ferroptosis-mediated IIR-ALI by regulating SLC7A11. Oxid Med Cell Longev. 2020;2020:5146982.
78 V Consoli, V Sorrenti, S Grosso, L Vanella. Heme oxygenase-1 signaling and redox homeostasis in physiopathological conditions. Biomolecules. 2021;11(4):589. doi:
79 H Wang, Q Wang, G Cai, et al. Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance. Acta Pharm Sin B. 2022;12:1871-1884.
80 E Petsouki, SNS Cabrera, EH Heiss. AMPK and NRF2: interactive players in the same team for cellular homeostasis? Free Radic Biol Med. 2022;190:75-93.
81 Z Zhao, Y Wang, Y Gao, et al. The PRAK-NRF2 axis promotes the differentiation of Th17 cells by mediating the redox homeostasis and glycolysis. Proc Natl Acad Sci USA. 2023;120:e2212613120.
82 D Lando, DJ Peet, JJ Gorman, DA Whelan, ML Whitelaw, RK Bruick. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002;16(12):1466-1471.
83 R Fukuda, H Zhang, Kim et al. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007;129:111-122.
84 D Tello, E Balsa, B Acosta-Iborra, et al. Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting Complex I activity. Cell Metab. 2011;14:768-779.
85 M Ivan. The EGLN-HIF O(2)-sensing system: multiple inputs and feedbacks. Mol Cell. 2017;66:772-779.
86 X Feng, S Wang, Z Sun, et al. Ferroptosis enhanced diabetic renal tubular injury via HIF-1α/HO-1 pathway in db/db mice. Front Endocrinol (Lausanne). 2021;12:626390.
87 Z Lin, J Song, Y Gao, et al. Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer. Redox Biol. 2022;52:102312.
88 MA Essers, S Weijzen, AM de Vries-Smits, et al. FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J. 2004;23:4802-4812.
89 M Putker, T Madl, HR Vos, et al. Redox-dependent control of FOXO/DAF-16 by transportin-1. Mol Cell. 2013;49:730-742.
90 LT Guo, SQ Wang, J Su, et al. Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. J Neuroinflammation. 2019;16(1):95.
91 Y Zhang, L Nie, K Xu, et al. SIRT6, a novel direct transcriptional target of FoxO3a, mediates colon cancer therapy. Theranostics. 2019;9:2380-2394.
92 Z Chen, C Zhao, P Liu, H Huang, S Zhang, X Wang. Antiapoptosis and autophagy effects of melatonin protect rat chondrocytes against oxidative stress via regulation of AMPK/Foxo3 pathways. Cartilage. 2021;13:1041S-1053S.
93 LCD Pomatto, PY Sun, K Yu, et al. Limitations to adaptive homeostasis in an hyperoxia-induced model of accelerated ageing. Redox Biol. 2019;24:101194.
94 L Casares, V García, M Garrido-Rodríguez, et al. Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020;28:101321.
95 D Namgaladze, DC Fuhrmann, B Brüne. Interplay of Nrf2 and BACH1 in inducing ferroportin expression and enhancing resistance of human macrophages towards ferroptosis. Cell Death Discov. 2022;8:327.
96 C Wang, L Zhang, M Cao, et al. Thioredoxin facilitates hepatocellular carcinoma stemness and metastasis by increasing BACH1 stability to activate the AKT/mTOR pathway. FASEB J. 2023;37:e22943.
97 S Xiong, L Dong, L Cheng. Neutrophils in cancer carcinogenesis and metastasis. J Hematol Oncol. 2021;14:173.
98 J Huang, Z Li, Y Hu, et al. Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis. J Neuroinflammation. 2022;19:124.
99 B Brüne, N Dehne, N Grossmann, et al. Redox control of inflammation in macrophages. Antioxid Redox Signal. 2013;19:595-637.
100 Y Lei, K Wang, L Deng, Y Chen, EC Nice, C Huang. Redox regulation of inflammation: old elements, a new story. Med Res Rev. 2015;35:306-340.
101 DN Doll, SL Rellick, TL Barr, X Ren, JW Simpkins. Rapid mitochondrial dysfunction mediates TNF-alpha-induced neurotoxicity. J Neurochem. 2015;132:443-451.
102 J Joffre, J Hellman. Oxidative stress and endothelial dysfunction in sepsis and acute inflammation. Antioxid Redox Signal. 2021;35:1291-1307.
103 B Andrade, C Jara-Gutiérrez, M Paz-Araos, MC Vázquez, P Díaz, P Murgas. The relationship between reactive oxygen species and the cGAS/STING signaling pathway in the inflammaging process. Int J Mol Sci. 2022;23(23):15182. doi:
104 SP Tang, XL Mao, YH Chen, LL Yan, LP Ye, SW Li. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Front Immunol. 2022;13:870239.
105 W Yu, X Wang, J Zhao, et al. Stat2-Drp1 mediated mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages. Redox Biol. 2020;37:101761.
106 SK Biswas. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev. 2016;2016:5698931.
107 Y Gong, X Cao, L Gong, W Li. Sulforaphane alleviates retinal ganglion cell death and inflammation by suppressing NLRP3 inflammasome activation in a rat model of retinal ischemia/reperfusion injury. Int J Immunopathol Pharmacol. 2019;33:2058738419861777.
108 AP West, GS Shadel. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17:363-375.
109 K Sharma, S Kumar, R Prakash, et al. Chebulinic acid alleviates LPS-induced inflammatory bone loss by targeting the crosstalk between reactive oxygen species/NFκB signaling in osteoblast cells. Free Radic Biol Med. 2023;194:99-113.
110 SJ Forrester, DS Kikuchi, MS Hernandes, Q Xu, KK Griendling. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res. 2018;122:877-902.
111 R Medzhitov. Origin and physiological roles of inflammation. Nature. 2008;454:428-435.
112 M Mittal, MR Siddiqui, K Tran, SP Reddy, AB Malik. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126-1167.
113 TR Hurd, M DeGennaro, R Lehmann. Redox regulation of cell migration and adhesion. Trends Cell Biol. 2012;22:107-115.
114 K Bedard, KH Krause. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245-313.
115 I Piotrowski, K Kulcenty, W Suchorska. Interplay between inflammation and cancer. Rep Pract Oncol Radiother. 2020;119:199-245.
116 M Philip, A Schietinger. CD8(+) T cell differentiation and dysfunction in cancer. Nat Rev Immunol. 2022;22:209-223.
117 DY Oh, L Fong. Cytotoxic CD4(+) T cells in cancer: expanding the immune effector toolbox. Immunity. 2021;54:2701-2711.
118 JS Dolina, N Van Braeckel-Budimir, GD Thomas. Salek-Ardakani S. CD8(+) T cell exhaustion in cancer. Front Immunol. 2021;12:715234.
119 ME Shaul, Z Fridlender. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol. 2019;16:601-620.
120 A Malfitano, S Pisanti, F Napolitano, S Di Somma, R Martinelli, G Portella. Tumor-associated macrophage status in cancer treatment. Cancers. 2020;12(7):1987. doi:
121 S Dallavalasa, NM Beeraka, CG Basavaraju, et al. The role of tumor associated macrophages (TAMs) in cancer progression, chemoresistance, angiogenesis and metastasis—current status. Curr Med Chem. 2021;28:8203-8236.
122 D Yuan, S Huang, E Berger, et al. Kupffer cell-derived Tnf triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer Cell. 2017;31(6):771-789. e6.
123 K Echizen, K Horiuchi, Y Aoki, et al. NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells. Oncogene. 2019;38(22):4250-4263.
124 S Bakewell, I Conde, Y Fallah, M McCoy, L Jin, AX Shajahan-Haq. Inhibition of DNA repair pathways and induction of ROS are potential mechanisms of action of the small molecule inhibitor BOLD-100 in breast cancer. Cancers. 2020;12(9):2647. doi:
125 SM Cheng, TY Lin, YC Chang, IW Lin, E Leung, CHA Cheung. YM155 and BIRC5 downregulation induce genomic instability via autophagy-mediated ROS production and inhibition in DNA repair. Pharmacol Res. 2021;166:105474.
126 K Frenkel. Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacol Ther. 1992;53:127-166.
127 CL Wilson, D Jurk, N Fullard, et al. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma. Nat Commun. 2015;6:6818.
128 V Butin-Israeli, TM Bui, HL Wiesolek, et al. Neutrophil-induced genomic instability impedes resolution of inflammation and wound healing. J Clin Invest. 2019;129:712-726.
129 C Ventura, JFS Pereira, P Matos, et al. Cytotoxicity and genotoxicity of MWCNT-7 and crocidolite: assessment in alveolar epithelial cells versus their coculture with monocyte-derived macrophages. Nanotoxicology. 2020;14(4):479-503.
130 PJ Borm, AM Knaapen, RP Schins, RW Godschalk, FJ Schooten. Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells. Environ Health Perspect. 1997;105(5):1089-1093. Suppl.
131 TT Borba, P Molz, DS Schlickmann, et al. Periodontitis: genomic instability implications and associated risk factors. Mutat Res Genet Toxicol Environ Mutagen. 2019;840:20-23.
132 NA Krump, J You. Molecular mechanisms of viral oncogenesis in humans. Nat Rev Microbiol. 2018;16:684-698.
133 G Tumurkhuu, S Chen, EN Montano, et al. Oxidative DNA damage accelerates skin inflammation in pristane-induced lupus model. Front Immunol. 2020;11:554725.
134 J Kay, E Thadhani, L Samson, B Engelward. Inflammation-induced DNA damage, mutations and cancer. DNA Repair (Amst). 2019;83:102673.
135 E Emerce, M Ghosh, D ?ner, et al. Carbon nanotube- and asbestos-induced DNA and RNA methylation changes in bronchial epithelial cells. Chem Res Toxicol. 2019;32:850-860.
136 D Costache, H Bejan, M Poenaru, R Costache. Skin cancer correlations in psoriatic patients. Cancers. 2023;15(9):2451. doi:
137 HS Kim, K Patel, K Muldoon-Jacobs, et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 2010;17(1):41-52.
138 GY Liou, P Storz. Reactive oxygen species in cancer. Free Radic Res. 2010;44:479-496.
139 M Assi. The differential role of reactive oxygen species in early and late stages of cancer. Am J Physiol Regul Integr Comp Physiol. 2017;313:R646-R653.
140 K Tuy, L Rickenbacker, AB Hjelmeland. Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance. Redox Biol. 2021;44:101953.
141 VI Sayin, MX Ibrahim, E Larsson, JA Nilsson, P Lindahl, MO Bergo. Antioxidants accelerate lung cancer progression in mice. Sci Transl Med. 2014;6:221ra15.
142 IS Harris, AE Treloar, S Inoue, et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell. 2015;27:211-222.
143 FL Sarmiento-Salinas, A Perez-Gonzalez, A Acosta-Casique, et al. Reactive oxygen species: role in carcinogenesis, cancer cell signaling and tumor progression. Life Sci. 2021;284:119942.
144 H Satoh, T Moriguchi, J Takai, M Ebina, M Yamamoto. Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis. Cancer Res. 2013;73(13):4158-4168.
145 S Tao, M Rojo de la Vega, E Chapman, A Ooi, DX Zhang. The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer. Mol Carcinog. 2018;57:182-192.
146 H Wang, X Liu, M Long, et al. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis. Sci Transl Med. 2016;8(334):334ra51.
147 JD Hayes, AT Dinkova-Kostova. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39(4):199-218.
148 LE Tebay, H Robertson, ST Durant, et al. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med. 2015;88:108-146. Pt B.
149 M Rojo de la Vega, E Chapman, DD Zhang. NRF2 and the hallmarks of cancer. Cancer Cell. 2018;34:21-43.
150 F He, X Ru, T Wen. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci. 2020;21(13):4777. doi:
151 P Canning, FJ Sorrell, AN Bullock. Structural basis of Keap1 interactions with Nrf2. Free Radic Biol Med. 2015;88:101-107.
152 M Eichenmüller, F Trippel, M Kreuder, et al. The genomic landscape of hepatoblastoma and their progenies with HCC-like features. J Hepatol. 2014;61(6):1312-1320.
153 B Padmanabhan, KI Tong, T Ohta, et al. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell. 2006;21:689-700.
154 R Wang, J An, F Ji, H Jiao, H Sun, D Zhou. Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem Biophys Res Commun. 2008;373:151-154.
155 M Komatsu, H Kurokawa, S Waguri, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12(3):213-223.
156 J Adam, E Hatipoglu, L O'Flaherty, et al. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell. 2011;20(4):524-537.
157 Y Mitsuishi, K Taguchi, Y Kawatani, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell. 2012;22(1):66-79.
158 GM DeNicola, PH Chen, E Mullarky, et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet. 2015;47(12):1475-1481.
159 M Luo, L Shang, MD Brooks, et al. Targeting breast cancer stem cell state equilibrium through modulation of redox signaling. Cell Metab. 2018;28(1):69-86.
160 IS Harris, JE Endress, JL Coloff, et al. Deubiquitinases maintain protein homeostasis and survival of cancer cells upon glutathione depletion. Cell Metab. 2019;29(5):1166-1181.
161 CJ Liu, JH Yang, FZ Huang, et al. Glutathione-s-transferase A 4 (GSTA4) suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting AKT pathway. Am J Transl Res. 2017;9:301-315.
162 O Herault, KJ Hope, E Deneault, et al. A role for GPx3 in activity of normal and leukemia stem cells. J Exp Med. 2012;209:895-901.
163 W Stafford, X Peng, MH Olofsson, et al. Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy. Sci Transl Med. 2018;10(428):eaaf7444. doi:
164 MK Cha, KH Suh, IH Kim. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma. J Exp Clin Cancer Res. 2009;28:93.
165 H Jiang, L Wu, M Mishra, HA Chawsheen, Q Wei. Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy. Am J Cancer Res. 2014;4:445-460.
166 A Glasauer, LA Sena, LP Diebold, AP Mazar, NS Chandel. Targeting SOD1 reduces experimental non–small-cell lung cancer. J Clin Invest. 2014;124(1):117-128.
167 L Torrente, N Prieto-Farigua, A Falzone, et al. Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to β-lapachone. Redox Biol. 2020;30:101440.
168 MD Cappellini, G Fiorelli. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;30(2):373-393.
169 MP Dore, A Davoli, N Longo, G Marras, GM Pes. Glucose-6-phosphate dehydrogenase deficiency and risk of colorectal cancer in Northern Sardinia: a retrospective observational study. Medicine (Baltimore). 2016;95:e5254.
170 AA Sablina, AV Budanov, GV Ilyinskaya, LS Agapova, JE Kravchenko, PM Chumakov. The antioxidant function of the p53 tumor suppressor. Nat Med. 2005;11:1306-1313.
171 P Gao, H Zhang, R Dinavahi, et al. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell. 2007;12:230-238.
172 K Le Gal, MX Ibrahim, C Wiel, et al. Antioxidants can increase melanoma metastasis in mice. Sci Transl Med. 2015;7(308):308re8.
173 SM Lippman, PJ Goodman, EA Klein, et al. Designing the selenium and vitamin E cancer prevention trial (SELECT). J Natl Cancer Inst. 2005;97:94-102.
174 B Anderton, R Camarda, S Balakrishnan, et al. MYC-driven inhibition of the glutamate-cysteine ligase promotes glutathione depletion in liver cancer. EMBO Rep. 2017;18:569-585.
175 DR Spitz, MT Kinter, RJ Roberts. Contribution of increased glutathione content to mechanisms of oxidative stress resistance in hydrogen peroxide resistant hamster fibroblasts. J Cell Physiol. 1995;165:600-609.
176 HH Bailey. L-S, R-buthionine sulfoximine: historical development and clinical issues. Chem Biol Interact. 1998;111-112:239-254.
177 HH Bailey, G Ripple, KD Tutsch, et al. Phase I study of continuous-infusion L-S,R-buthionine sulfoximine with intravenous melphalan. J Natl Cancer Inst. 1997;89:1789-1796.
178 S Nishizawa, H Araki, Y Ishikawa, et al. Low tumor glutathione level as a sensitivity marker for glutamate-cysteine ligase inhibitors. Oncol Lett. 2018;15(6):8735-8743.
179 J Luo, NL Solimini, SJ Elledge. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell. 2009;136:823-837.
180 LL Policastro, IL Iba?ez, C Notcovich, HA Duran, OL Podhajcer. The tumor microenvironment: characterization, redox considerations, and novel approaches for reactive oxygen species-targeted gene therapy. Antioxid Redox Signal. 2013;19:854-895.
181 VI Seledtsov, AG Goncharov, GV Seledtsova. Clinically feasible approaches to potentiating cancer cell-based immunotherapies. Hum Vaccin Immunother. 2015;11:851-869.
182 S Cemerski, A Cantagrel, JP Van Meerwijk, P Romagnoli. Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem. 2002;277:19585-19593.
183 T Maj, W Wang, J Crespo, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18:1332-1341.
184 LA Sena, S Li, A Jairaman, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38(2):225-236.
185 M Kaminski, M Kiessling, D Süss, PH Krammer, K Gülow. Novel role for mitochondria: protein kinase Ctheta-dependent oxidative signaling organelles in activation-induced T-cell death. Mol Cell Biol. 2007;27:3625-3639.
186 MM Kamiński, SW Sauer, M Kamiński, et al. T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep. 2012;2(5):1300-1315.
187 JU Lee, LK Kim, JM Choi. Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases. Front Immunol. 2018;9:2747.
188 M Vaeth, S Feske. NFAT control of immune function: new frontiers for an abiding trooper. F1000Res. 2018;7:260.
189 D Mougiakakos, CC Johansson, R Kiessling. Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death. Blood. 2009;113(15):3542-3545.
190 PH Krammer, R Arnold, IN Lavrik. Life and death in peripheral T cells. Nat Rev Immunol. 2007;7:532-542.
191 SH Jackson, S Devadas, J Kwon, LA Pinto, MS Williams. T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat Immunol. 2004;5(8):818-827.
192 J Kwon, KE Shatynski, H Chen, et al. The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling. Sci Signal. 2010;3:ra59.
193 AV Belikov, B Schraven, L Simeoni. T cells and reactive oxygen species. J Biomed Sci. 2015;22:85.
194 L Lucca, M Dominguez-Villar. Modulation of regulatory T cell function and stability by co-inhibitory receptors. Nat Rev Immunol. 2020;20:680-693.
195 O Efimova, P Szankasi, TW Kelley. Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PLoS One. 2011;6(1):e16013.
196 HR Kim, A Lee, EJ Choi, et al. Reactive oxygen species prevent imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function. PLoS One. 2014;9(3):e91146.
197 Y Kunisada, S Eikawa, N Tomonobu, et al. Attenuation of CD4(+)CD25(+) regulatory T cells in the tumor microenvironment by metformin, a type 2 diabetes drug. EBioMedicine. 2017;25:154-164.
198 SE Weinberg, BD Singer, EM Steinert, et al. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature. 2019;565(7740):495-499.
199 X Yu, Y Lao, XL Teng, et al. SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nat Commun. 2018;9:3157.
200 HR Kim, A Lee, EJ Choi, et al. Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function. PLoS One. 2014;9(4):e95332.
201 U Sivagnanalingam, PL Beatty, OJ Finn. Myeloid derived suppressor cells in cancer, premalignancy and inflammation: a roadmap to cancer immunoprevention. Mol Carcinog. 2020;59(7):852-861.
202 DI Gabrilovich, S Nagaraj. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162-174.
203 CM Diaz-Montero, ML Salem, MI Nishimura, E Garrett-Mayer, DJ Cole, AJ Montero. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58:49-59.
204 CA Corzo, MJ Cotter, P Cheng, et al. Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol. 2009;182:5693-5701.
205 S Kusmartsev, DI Gabrilovich. Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol. 2003;74:186-196.
206 X Chen, M Song, B Zhang, Y Zhang. Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxid Med Cell Longev. 2016;2016:1580967.
207 H Zhang, ZL Li, SB Ye, et al. Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator. Cancer Immunol Immunother. 2015;64:1587-1599.
208 J Wei, M Zhang, J Zhou. Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species. Psychiatry Res. 2015;228(3):695-701.
209 DW Beury, KA Carter, C Nelson, et al. Myeloid-derived suppressor cell survival and function are regulated by the transcription factor Nrf2. J Immunol. 2016;196:3470-3478.
210 PJ Murray, JE Allen, SK Biswas, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14-20.
211 RD Leek, CE Lewis, R Whitehouse, M Greenall, J Clarke, AL Harris. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996;56:4625-4629.
212 A Mantovani, F Marchesi, A Malesci, L Laghi, P Allavena. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399-416.
213 BZ Qian, JW Pollard. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39-51.
214 S Tiainen, R Tumelius, K Rilla, et al. High numbers of macrophages, especially M2-like (CD163-positive), correlate with hyaluronan accumulation and poor outcome in breast cancer. Histopathology. 2015;66(6):873-883.
215 TA Klingen, Y Chen, H Aas, E Wik, LA Akslen. Tumor-associated macrophages are strongly related to vascular invasion, non-luminal subtypes, and interval breast cancer. Hum Pathol. 2017;69:72-80.
216 L Li, J Chen, G Xiong, DK St Clair, W Xu, R Xu. Increased ROS production in non-polarized mammary epithelial cells induces monocyte infiltration in 3D culture. J Cell Sci. 2017;130:190-202.
217 X Tang, C Mo, Y Wang, D Wei, H Xiao. Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology. 2013;138:93-104.
218 D Hackel, D Pflücke, A Neumann, et al. The connection of monocytes and reactive oxygen species in pain. PLoS One. 2013;8:e63564.
219 HY Tan, NX Wang, S Li, M Hong, X Wang, YX Feng. The reactive oxygen species in macrophage polarization: reflecting its dual role in progression and treatment of human diseases. Oxid Med Cell Longev. 2016;2016:2795090.
220 Y Zhang, S Choksi, K Chen, Y Pobezinskaya, I Linnoila, ZG Liu. ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res. 2013;23:898-914.
221 B Griess, S Mir, K Datta, M Teoh-Fitzgerald. Scavenging reactive oxygen species selectively inhibits M2 macrophage polarization and their pro-tumorigenic function in part, via Stat3 suppression. Free Radic Biol Med. 2020;147:48-60.
222 JR Gordon, Y Ma, L Churchman, SA Gordon, W Dawicki. Regulatory dendritic cells for immunotherapy in immunologic diseases. Front Immunol. 2014;5:7.
223 F Geissmann, MG Manz, S Jung, MH Sieweke, M Merad, K Ley. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656-661.
224 LM Paardekooper, I Dingjan, PTA Linders, et al. Human monocyte-derived dendritic cells produce millimolar concentrations of ROS in phagosomes per second. Front Immunol. 2019;10:1216.
225 LM Paardekooper, W Vos, G van den Bogaart. Oxygen in the tumor microenvironment: effects on dendritic cell function. Oncotarget. 2019;10:883-896.
226 AR Mantegazza, A Savina, M Vermeulen, et al. NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells. Blood. 2008;112:4712-4722.
227 A Savina, C Jancic, S Hugues, et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell. 2006;126:205-218.
228 M Oberkampf, C Guillerey, J Mouriès, et al. Mitochondrial reactive oxygen species regulate the induction of CD8(+) T cells by plasmacytoid dendritic cells. Nat Commun. 2018;9:2241.
229 CA Chougnet, RI Thacker, HM Shehata, et al. Loss of phagocytic and antigen cross-presenting capacity in aging dendritic cells is associated with mitochondrial dysfunction. J Immunol. 2015;195(6):2624-2632.
230 JR Cubillos-Ruiz, PC Silberman, MR Rutkowski, et al. ER stress sensor XBP1 controls anti-taumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161:1527-1538.
231 AM Abel, C Yang, MS Thakar, S Malarkannan. Natural killer cells: development, maturation, and clinical utilization. Front Immunol. 2018;9:1869.
232 K Imai, S Matsuyama, S Miyake, K Suga, K Nakachi. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356:1795-1799.
233 A Betten, C Dahlgren, UH Mellqvist, S Hermodsson, K Hellstrand. Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin. J Leukoc Biol. 2004;75:1111-1115.
234 Y Yang, SY Neo, Z Chen, et al. Thioredoxin activity confers resistance against oxidative stress in tumor-infiltrating NK cells. J Clin Invest. 2020;130:5508-5522.
235 E Aydin, J Johansson, FH Nazir, K Hellstrand, A Martner. Role of NOX2-derived reactive oxygen species in NK cell-mediated control of murine melanoma metastasis. Cancer Immunol Res. 2017;5:804-811.
236 K Mimura, LF Kua, N Shimasaki, et al. Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress. Cancer Immunol Immunother. 2017;66:605-613.
237 SB Coffelt, MD Wellenstein, KE de Visser. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016;16(7):431-446.
238 S Jaillon, AX Ponzetta, D Di Mitri, A Santoni, R Bonecchi, AX Mantovani. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20:485-503.
239 Z Granot, E Henke, EA Comen, TA King, L Norton, R Benezra. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20:300-314.
240 M Gershkovitz, Y Caspi, T Fainsod-Levi, et al. TRPM2 mediates neutrophil killing of disseminated tumor cells. Cancer Res. 2018;78:2680-2690.
241 P Li, M Lu, J Shi, et al. Dual roles of neutrophils in metastatic colonization are governed by the host NK cell status. Nat Commun. 2020;11:4387.
242 S Mensurado, M Rei, T Lan?a, et al. Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress. PLoS Biol. 2018;16(5):e2004990.
243 ? Canli, AM Nicolas, J Gupta, et al. Myeloid cell-derived reactive oxygen species induce epithelial mutagenesis. Cancer Cell. 2017;32:869-883. e5.
244 SK Wculek, VL Bridgeman, F Peakman, I Malanchi. Early neutrophil responses to chemical carcinogenesis shape long-term lung cancer susceptibility. iScience. 2020;23:101277.
245 M Inoue, R Nakashima, M Enomoto, et al. Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis. Nat Commun. 2018;9:5116.
246 K Furukawa, R Tengler, M Nakamura, et al. B lymphoblasts show oxidase activity in response to cross-linking of surface IgM and HLA-DR. Scand J Immunol. 1992;35(5):561-567.
247 M Kondo. Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. Immunol Rev. 2010;238:37-46.
248 TW LeBien, TF Tedder. B lymphocytes: how they develop and function. Blood. 2008;112(5):1570-1580.
249 H Zhang, L Wang, Y Chu. Reactive oxygen species: the signal regulator of B cell. Free Radic Biol Med. 2019;142:16-22.
250 Y Suzuki, Y Ono. Involvement of reactive oxygen species produced via NADPH oxidase in tyrosine phosphorylation in human B- and T-lineage lymphoid cells. Biochem Biophys Res Commun. 1999;255:262-267.
251 EK Kim, HS Seo, MJ Chae, et al. Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. Gene Ther. 2014;21:106-114.
252 M Candolfi, JF Curtin, K Yagiz, et al. B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma. Neoplasia. 2011;13:947-960.
253 R Jitschin, AD Hofmann, H Bruns, et al. Mitochondrial metabolism contributes to oxidative stress and reveals therapeutic targets in chronic lymphocytic leukemia. Blood. 2014;123:2663-2672.
254 K Fidyt, A Pastorczak, A Goral, et al. Targeting the thioredoxin system as a novel strategy against B-cell acute lymphoblastic leukemia. Mol Oncol. 2019;13(5):1180-1195.
255 G Xiao, LN Chan, L Klemm, et al. B-cell-specific diversion of glucose carbon utilization reveals a unique vulnerability in B cell malignancies. Cell. 2018;173:470-484. e18.
256 C Robert. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020;11:3801.
257 Q Zhang, L Wu, S Liu, et al. Moderating hypoxia and promoting immunogenic photodynamic therapy by HER-2 nanobody conjugate nanoparticles for ovarian cancer treatment. Nanotechnology. 2021;32(42). doi:
258 D Wang, T Wang, H Yu, et al. Engineering nanoparticles to locally activate T cells in the tumor microenvironment. Sci Immunol. 2019;4(37):eaau6584. doi:
259 K Chamoto, PS Chowdhury, A Kumar, et al. Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity. Proc Natl Acad Sci USA. 2017;114:E761-E770.
260 J Guo, Z Yu, D Sun, Y Zou, Y Liu, L Huang. Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma. Mol Cancer. 2021;20:10.
261 S Ma, X Li, X Wang, et al. Current progress in CAR-T cell therapy for solid tumors. Int J Biol Sci. 2019;15:2548-2560.
262 X Zhang, L Zhu, H Zhang, S Chen, Y Xiao. CAR-T cell therapy in hematological malignancies: current opportunities and challenges. Front Immunol. 2022;13:927153.
263 J Liu, S Yang, B Cao, et al. Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes. J Hematol Oncol. 2021;14:21.
264 JAC van Bruggen, AWJ Martens, JA Fraietta, et al. Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8(+) T cells and impede CAR T-cell efficacy. Blood. 2019;134:44-58.
265 HJ Yoo, Y Liu, L Wang, et al. Tumor-specific reactive oxygen species accelerators improve chimeric antigen receptor T cell therapy in B cell malignancies. Int J Mol Sci. 2019;20(10):22469. doi:
266 J Jiang, Z Peng, J Wang, et al. C-reactive protein impairs immune response of CD8(+) T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma. J Immunother Cancer. 2023;11(10):e007593. doi:
267 R Zhang, Q Liu, S Zhou, H He, M Zhao, W Ma. Mesenchymal stem cell suppresses the efficacy of CAR-T toward killing lymphoma cells by modulating the microenvironment through stanniocalcin-1. Elife. 2023;12:e82934. doi:
268 J Liu, M Fu, M Wang, D Wan, Y Wei, X Wei. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J Hematol Oncol. 2022;15(1):28.
269 W Yan, W Chen, L Huang. Reactive oxygen species play a central role in the activity of cationic liposome based cancer vaccine. J Control Release. 2008;130:22-28.
270 H Pan, H Shi, P Fu, P Shi, J Yang. Liposomal dendritic cell vaccine in breast cancer immunotherapy. ACS Omega. 2021;6:3991-3998.
271 Y Zhang, S Ma, X Liu, et al. Supramolecular assembled programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy. Adv Mater. 2021;33:e2007293.
272 CX Xu, H Hong, Y Lee, et al. Efficient lymph node-targeted delivery of personalized cancer vaccines with reactive oxygen species-inducing reduced graphene oxide nanosheets. ACS Nano. 2020;14:13268-13278.
273 S Kwiatkowski, B Knap, D Przystupski, et al. Photodynamic therapy—mechanisms, photosensitizers and combinations. Biomed Pharmacother. 2018;106:1098-1107.
274 DW Felsher. Cancer revoked: oncogenes as therapeutic targets. Nat Rev Cancer. 2003;3(5):375-380.
275 Z Li, L Zhu, H Sun, et al. Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot. Proc Natl Acad Sci USA. 2020;117:32962-32969.
276 L Wang, Y Liu, H Liu, et al. The therapeutic significance of the novel photodynamic material TPE-IQ-2O in tumors. Aging (Albany NY). 2020;13:1383-1409.
277 C He, X Duan, N Guo, et al. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat Commun. 2016;7:12499.
278 S He, S Lu, S Liu, et al. Spatiotemporally controlled O(2) and singlet oxygen self-sufficient nanophotosensitizers enable the in vivo high-yield synthesis of drugs and efficient hypoxic tumor therapy. Chem Sci. 2020;11:8817-8827.
279 K Ni, G Lan, Y Song, Z Hao, W Lin. Biomimetic nanoscale metal-organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy. Chem Sci. 2020;11:7641-7653.
280 A Sahu, K Min, J Jeon, HS Yang, G Tae. Catalytic nanographene oxide with hemin for enhanced photodynamic therapy. J Control Release. 2020;326:442-454.
281 Y Kang, L Lei, C Zhu, H Zhang, L Mei, X Ji. Piezo-photocatalytic effect mediating reactive oxygen species burst for cancer catalytic therapy. Mater Horiz. 2021;8:2273-2285.
282 Y Wei, Z Wang, J Yang, et al. Reactive oxygen species /photothermal therapy dual-triggered biomimetic gold nanocages nanoplatform for combination cancer therapy via ferroptosis and tumor-associated macrophage repolarization mechanism. J Colloid Interface Sci. 2022;606:1950-1965.
283 R Canaparo, F Foglietta, T Limongi, L Serpe. Biomedical applications of reactive oxygen species generation by metal nanoparticles. Materials. 2020;14(1):53. doi:
284 H Ranji-Burachaloo, PA Gurr, DE Dunstan, G Qiao. Cancer treatment through nanoparticle-facilitated fenton reaction. ACS Nano. 2018;12(12):11819-11837.
285 W Wu, Y Pu, JX Shi. Dual size/charge-switchable nanocatalytic medicine for deep tumor therapy. Adv Sci (Weinh). 2021;8:2002816.
286 D Ding, Y Feng, R Qin, et al. Mn(3+)-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment. Theranostics. 2021;11:7439-7449.
287 M Huo, L Wang, Y Wang, Y Chen, JX Shi. Nanocatalytic tumor therapy by single-atom catalysts. ACS Nano. 2019;13:2643-2653.
288 Z Gu, T Liu, J Tang, et al. Mechanism of iron oxide-induced macrophage activation: the impact of composition and the underlying signaling pathway. J Am Chem Soc. 2019;141:6122-6126.
289 W Li, J Yang, L Luo, et al. Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death. Nat Commun. 2019;10:3349.
290 K Ni, T Luo, GT Nash, W Lin. Nanoscale metal-organic frameworks for cancer immunotherapy. Acc Chem, Res. 2020;53(9):1739-1748.
291 J Xiang, Y Li, Y Zhang, et al. Polyphenol-cisplatin complexation forming core-shell nanoparticles with improved tumor accumulation and dual-responsive drug release for enhanced cancer chemotherapy. J Control Release. 2021;330:992-1003.
292 KT Lee, YJ Lu, FL Mi, et al. Catalase-modulated heterogeneous fenton reaction for selective cancer cell eradication: snFe(2)O(4) nanocrystals as an effective reagent for treating lung cancer cells. ACS Appl Mater Interfaces. 2017;9(2):1273-1279.
293 A Le, ZE Stine, C Nguyen, et al. Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter. Proc Natl Acad Sci USA. 2014;111:12486-12491.
294 WL Rumsey, C Schlosser, EM Nuutinen, M Robiolio, DF Wilson. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem. 1990;265:15392-15402.
295 R DeBerardinis, N Chandel. We need to talk about the Warburg effect. Nat Metab. 2020;2(2):127-129.
296 Q Yang, L Wang, J Liu, W Cao, Q Pan, MX Li. Targeting the complex I and III of mitochondrial electron transport chain as a potentially viable option in liver cancer management. Cell Death Discov. 2021;7(1):293.
297 S Chen, L Sun, K Koya, et al. Syntheses and antitumor activities of N'1,N'3-dialkyl-N'1,N'3-di-(alkylcarbonothioyl) malonohydrazide: the discovery of elesclomol. Bioorg Med Chem Lett. 2013;23(18):5070-5076.
298 M Nagai, NH Vo, L Shin Ogawa, et al. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 2012;52:2142-2150.
299 P Tsvetkov, S Coy, B Petrova, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375:1254-1261.
300 T Pham, CL MacRae, SC Broome, et al. MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men. Eur J Appl Physiol. 2020;120(7):1657-1669.
301 HS Qsee, PK Tambe, S De, S Bharati. MitoQ demonstrates connexin- and p53-mediated cancer chemoprevention in N-nitrosodiethylamine-induced hepatocarcinogenesis rodent model. Toxicol Appl Pharmacol. 2022;453:116211.
302 L Wang, JY Chan, X Zhou, et al. A novel agent enhances the chemotherapeutic efficacy of doxorubicin in MCF-7 breast cancer cells. Front Pharmacol. 2016;7:249.
303 MS Weng, JH Chang, WY Hung, YC Yang, M Chien. The interplay of reactive oxygen species and the epidermal growth factor receptor in tumor progression and drug resistance. J Exp Clin Cancer Res. 2018;37:61.
304 Y Miyata, T Matsuo, Y Sagara, K Ohba, K Ohyama, H Sakai. A mini-review of reactive oxygen species in urological cancer: correlation with NADPH oxidases, angiogenesis, and apoptosis. Int J Mol Sci. 2017;18(10):2214. doi:
305 K Shanmugasundaram, BK Nayak, WE Friedrichs, D Kaushik, R Rodriguez, K Block. NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance. Nat Commun. 2017;8(1):997.
306 R Ameziane-El-Hassani, M Schlumberger, C Dupuy. NADPH oxidases: new actors in thyroid cancer? Nat Rev Endocrinol. 2016;12(8):485-494.
307 M H?ll, R Koziel, G Sch?fer, et al. ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells. Mol Carcinog. 2016;55:27-39.
308 P Wang, Q Shi, WH Deng, et al. Relationship between expression of NADPH oxidase 2 and invasion and prognosis of human gastric cancer. World J Gastroenterol. 2015;21(20):6271-6279.
309 DE Green, TC Murphy, BY Kang, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol. 2012;47:718-726.
310 C Zeng, Q Wu, J Wang, et al. NOX4 supports glycolysis and promotes glutamine metabolism in non-small cell lung cancer cells. Free Radic Biol Med. 2016;101:236-248.
311 T Yamamoto, H Nakano, K Shiomi, et al. Identification and characterization of a novel NADPH oxidase 1 (Nox1) inhibitor that suppresses proliferation of colon and stomach cancer cells. Biol Pharm Bull. 2018;41(3):419-426.
312 P Wang, YC Sun, WH Lu, P Huang, Y Hu. Selective killing of Kras-transformed pancreatic cancer cells by targeting NAD(P)H oxidase. Chin J Cancer. 2015;34:166-176.
313 L Dai, MC Noverr, C Parsons, JA Kaleeba, Z Qin. xCT, not just an amino-acid transporter: a multi-functional regulator of microbial infection and associated diseases. Front Microbiol. 2015;6:120.
314 K Sugano, K Maeda, H Ohtani, H Nagahara, M Shibutani, K Hirakawa. Expression of xCT as a predictor of disease recurrence in patients with colorectal cancer. Anticancer Res. 2015;35(2):677-682.
315 A Shiozaki, D Iitaka, D Ichikawa, et al. xCT, component of cysteine/glutamate transporter, as an independent prognostic factor in human esophageal squamous cell carcinoma. J Gastroenterol. 2014;49(5):853-863.
316 RM Drayton, E Dudziec, S Peter, et al. Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin Cancer Res. 2014;20:1990-2000.
317 R Oerlemans, J Vink, BA Dijkmans, et al. Sulfasalazine sensitises human monocytic/macrophage cells for glucocorticoids by upregulation of glucocorticoid receptor alpha and glucocorticoid induced apoptosis. Ann Rheum Dis. 2007;66:1289-1295.
318 Y Song, J Jang, TH Shin, et al. Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2017;36:38.
319 AN Pham, PE Blower, O Alvarado, R Ravula, PW Gout, Y Huang. Pharmacogenomic approach reveals a role for the x(c)- cystine/glutamate antiporter in growth and celastrol resistance of glioma cell lines. J Pharmacol Exp Ther. 2010;332:949-958.
320 E Singer, J Judkins, N Salomonis, et al. Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma. Cell Death Dis. 2015;6:e1601.
321 JL Roh, EH Kim, HJ Jang, JY Park, D Shin. Induction of ferroptotic cell death for overcoming cisplatin resistance of head and neck cancer. Cancer Lett. 2016;381:96-103.
322 AA Turanov, S Kehr, SM Marino, et al. Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets. Biochem J. 2010;430:285-293.
323 G Zhang, W Wang, C Yao, J Ren, S Zhang, M Han. Salinomycin overcomes radioresistance in nasopharyngeal carcinoma cells by inhibiting Nrf2 level and promoting ROS generation. Biomed Pharmacother. 2017;91:147-154.
324 ES Arnér. Focus on mammalian thioredoxin reductases–important selenoproteins with versatile functions. Biochim Biophys Acta. 2009;1790:495-526.
325 ES Arnér, A Holmgren. The thioredoxin system in cancer. Semin Cancer Biol. 2006;16(6):420-426.
326 SE Eriksson, S Prast-Nielsen, E Flaberg, L Szekely, ES Arnér. High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy. Free Radic Biol Med. 2009;47:1661-1671.
327 CR Myers. Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase. Free Radic Biol Med. 2016;91:81-92.
328 C Roder, MJ Thomson. Auranofin: repurposing an old drug for a golden new age. Drugs R D. 2015;15:13-20.
329 JJ Liu, Q Liu, HL Wei, J Yi, HS Zhao, LP Gao. Inhibition of thioredoxin reductase by auranofin induces apoptosis in adriamycin-resistant human K562 chronic myeloid leukemia cells. Pharmazie. 2011;66:440-444.
330 GX Hou, PP Liu, S Zhang, et al. Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis. Cell Death Dis. 2018;9(2):89.
331 L Wang, Z Yang, J Fu, et al. Ethaselen: a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent. Free Radic Biol Med. 2012;52:898-908.
332 Q Tan, J Li, HW Yin, et al. Augmented antitumor effects of combination therapy of cisplatin with ethaselen as a novel thioredoxin reductase inhibitor on human A549 cell in vivo. Invest New Drugs. 2010;28(3):205-215.
333 SF Ye, Y Yang, L Wu, WW Ma, HH Zeng. Ethaselen: a novel organoselenium anticancer agent targeting thioredoxin reductase 1 reverses cisplatin resistance in drug-resistant K562 cells by inducing apoptosis. J Zhejiang Univ Sci B. 2017;18:373-382.
334 L Zeng, Y Chen, J Liu, et al. Ruthenium(II) complexes with 2-phenylimidazo[4,5-f][1,10]phenanthroline derivatives that strongly combat cisplatin-resistant tumor cells. Sci Rep. 2016;6:19449.
335 P Zheng, C Zhou, L Lu, B Liu, Y Ding. Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy. J Exp Clin Cancer Res. 2022;41:271.
336 SJ O'Day, AM Eggermont, V Chiarion-Sileni, et al. Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma. J Clin Oncol. 2013;31(9):1211-1218.
337 PJ Siska, KE Beckermann, FM Mason, et al. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. J C I Insight. 2017;2(12):e93411. doi:
338 N Yoon, H Lee, S Kim, et al. Mitoquinone inactivates mitochondrial chaperone TRAP1 by blocking the client binding site. J Am Chem Soc. 2021;143(47):19684-19696.
339 Y Masoumi-Ardakani, H Najafipour, H Nasri, S Aminizadeh, S Jafari, D Moflehi. Effect of combined endurance training and MitoQ on cardiac function and serum level of antioxidants, NO, miR-126, and miR-27a in hypertensive individuals. Biomed Res Int. 2022;2022:8720661.
340 L Wang, X Zhang, G Cui, et al. A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II. Oncotarget. 2016;7:32054-32064.
341 X Zhou, A Wang, L Wang, et al. A danshensu-tetramethylpyrazine conjugate DT-010 overcomes multidrug resistance in human breast cancer. Front Pharmacol. 2019;10:722.
342 D Deliyanti, JL Wilkinson-Berka. Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate neuroglial cell inflammation in the retina. J Neuroinflammation. 2015;12:136.
343 J Jha, A Dai, J Garzarella, et al. Independent of renox, NOX5 promotes renal inflammation and fibrosis in diabetes by activating ROS-sensitive pathways. Diabetes. 2022;71:1282-1298.
344 H Zheng, N Xu, Z Zhang, F Wang, J Xiao, X Ji. Setanaxib (GKT137831) ameliorates doxorubicin-induced cardiotoxicity by inhibiting the NOX1/NOX4/reactive oxygen species/MAPK pathway. Front Pharmacol. 2022;13:823975.
345 D Jones, M Carbone, P Invernizzi, et al. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun. 2023;7:e0057.
346 YC Chung, JY Baek, S Kim, et al. Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson's disease. Exp Mol Med. 2017;49:e298.
347 RM Stevens, J Ervin, J Nezzer, et al. Randomized, double-blind, placebo-controlled trial of intraarticular trans-capsaicin for pain associated with osteoarthritis of the knee. Arthritis Rheumatol. 2019;71:1524-1533.
348 A Islam, AJ Su, ZM Zeng, P Chueh, MH Lin. Capsaicin targets tNOX (ENOX2) to inhibit G1 cyclin/CDK complex, as assessed by the cellular thermal shift assay (CETSA). Cells. 2019;8(10):1275. doi:
349 C Hacioglu. Capsaicin inhibits cell proliferation by enhancing oxidative stress and apoptosis through SIRT1/NOX4 signaling pathways in HepG2 and HL-7702 cells. J Biochem Mol Toxicol. 2022;36(3):e22974.
350 N Yagoda, M von Rechenberg, E Zaganjor, et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007;447:864-868.
351 Y Ye, A Chen, L Li, et al. Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification. Kidney Int. 2022;102:1259-1275.
352 K Ogihara, E Kikuchi, S Okazaki, et al. Sulfasalazine could modulate the CD44v9-xCT system and enhance cisplatin-induced cytotoxic effects in metastatic bladder cancer. Cancer Sci. 2019;110(4):1431-1441.
353 H Yu, C Yang, L Jian, et al. Sulfasalazine?induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep. 2019;42(2):826-838.
354 JL Roh, EH Kim, H Jang, D Shin. Aspirin plus sorafenib potentiates cisplatin cytotoxicity in resistant head and neck cancer cells through xCT inhibition. Free Radic Biol Med. 2017;104:1-9.
355 I Fujikawa, T Ando, M Suzuki-Karasaki, M Suzuki-Karasaki, T Ochiai, Y Suzuki-Karasaki. Aspirin induces mitochondrial Ca(2+) remodeling in tumor cells via ROS?depolarization?voltage-gated Ca(2+) entry. Int, J Mol Sci. 2020;21(13):4771. doi:
356 NH Kim, HJ Park, MK Oh, IS Kim. Antiproliferative effect of gold(I) compound auranofin through inhibition of STAT3 and telomerase activity in MDA-MB 231 human breast cancer cells. B M B Rep. 2013;46(1):59-64.
357 C Fan, W Zheng, X Fu, X Li, YS Wong, T Chen. Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo. Cell Death Dis. 2014;5:e1191.
358 X Zheng, Y Chen, M Bai, et al. The antimetastatic effect and underlying mechanisms of thioredoxin reductase inhibitor ethaselen. Free Radic Biol Med. 2019;131:7-17.
359 Y Li, Q Wu, G Yu, et al. Polypyridyl Ruthenium(II) complex-induced mitochondrial membrane potential dissipation activates DNA damage-mediated apoptosis to inhibit liver cancer. Eur J Med Chem. 2019;164:282-291.
360 Z Luo, L Yu, F Yang, et al. Ruthenium polypyridyl complexes as inducer of ROS-mediated apoptosis in cancer cells by targeting thioredoxin reductase. Metallomics. 2014;6(8):1480-1490.
361 JC Chen, Y Zhang, XM Jie, et al. Ruthenium(II) salicylate complexes inducing ROS-mediated apoptosis by targeting thioredoxin reductase. J Inorg Biochem. 2019;193:112-123.
PDF

Accesses

Citations

Detail

Sections
Recommended

/