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Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Glutathione, an Antioxidant Tripeptide: Dual Roles in Carcinogenesis and Chemoprevention

Author(s): Arunaksharan Narayanankutty*, Joice Tom Job and Vinayak Narayanankutty

Volume 20 , Issue 9 , 2019

Page: [907 - 917] Pages: 11

DOI: 10.2174/1389203720666190206130003

Price: $65


Glutathione (GSH or reduced glutathione) is a tripeptide of gamma-Glutamyl-cysteinylglycine and the predominant intracellular antioxidant in many organisms including humans. GSH and associated enzymes are controlled by a transcription factor-nuclear factor-2 related erythroid factor-2 (Nrf2). In cellular milieu, GSH protects the cells essentially against a wide variety of free radicals including reactive oxygen species, lipid hydroperoxides, xenobiotic toxicants, and heavy metals. It has two forms, the reduced form or reduced glutathione (GSH) and oxidized form (GSSG), where two GSH moieties combine by sulfhydryl bonds. Glutathione peroxidase (GPx) and glutathione-s-transferase (GST) essentially perform the detoxification reactions using GSH, converting it into GSSG. Glutathione reductase (GR) operates the salvage pathway by converting GSSG to GSH with the expense of NADPH and restores the cellular GSH pool. Hence, GSH and GSH-dependent enzymes are necessary for maintaining the normal redox balance in the body and help in cell survival under stress conditions. In addition, GST removes various carcinogenic compounds offering a chemopreventive property, whereas the GSH system plays a significant role in regulating the cellular survival by offering redox stability in a variety of cancers including prostate, lung, breast, and colon cancer. Studies have also indicated that GSH inhibitors, such as buthionine sulfoximine, improve the chemo-sensitivity in cancer cells. In addition, GSH and dependent enzymes provide a survival advantage for cancer cells against chemotherapeutic drugs and radiotherapy.

Keywords: Glutathione, chemoprevention, carcinogenesis, drug resistance, glutathione-s-transferase, antioxidant.

Graphical Abstract
Cheseto, X.; Kachigamba, D.L.; Ekesi, S.; Ndung’u, M.; Teal, P.E.A.; Beck, J.J.; Torto, B. Identification of the ubiquitous antioxidant tripeptide glutathione as a fruit fly semiochemical. J. Agric. Food Chem., 2017, 65(39), 8560-8568.
Meredith, M.J.; Reed, D.J. Status of the mitochondrial pool of glutathione in the isolated hepatocyte. J. Biol. Chem., 1982, 257(7), 3747-3753.
Hwang, C.; Sinskey, A.J.; Lodish, H.F. Oxidized redox state of glutathione in the endoplasmic reticulum. Science, 1992, 257(5076), 1496-1502.
Sheehan, D.; Meade, G.; Foley, V.M.; Dowd, C.A. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem. J., 2001, 360(Pt 1), 1-16.
Bae, Y.A.; Cai, G.B.; Kim, S.H.; Zo, Y.G.; Kong, Y. Modular evolution of glutathione peroxidase genes in association with different biochemical properties of their encoded proteins in invertebrate animals. BMC Evol. Biol., 2009, 9, 72.
Balendiran, G.K.; Dabur, R.; Fraser, D. The role of glutathione in cancer. Cell Biochem. Funct., 2004, 22(6), 343-352.
Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull., 2017, 7(3), 339-348.
Tang, L.; Wang, W.; Zhou, W.; Cheng, K.; Yang, Y.; Liu, M.; Cheng, K.; Wang, W. Three-pathway combination for glutathione biosynthesis in Saccharomyces cerevisiae. Microb. Cell Fact., 2015, 14(1), 139.
Morales, Pantoja I.E.; Hu, C.L.; Perrone-Bizzozero, N.I.; Zheng, J.; Bizzozero, O.A. Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis. J. Neurochem., 2016, 139(4), 640-650.
Liang, M.; Wang, Z.; Li, H.; Cai, L.; Pan, J.; He, H.; Wu, Q.; Tang, Y.; Ma, J.; Yang, L. l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway. Food Chem. Toxicol., 2018, 115, 315-328.
Espinosa-Diez, C.; Miguel, V.; Mennerich, D.; Kietzmann, T.; Sánchez-Pérez, P.; Cadenas, S.; Lamas, S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol., 2015, 6, 183-197.
Ma, Q. Role of nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol., 2013, 53, 401-426.
Rojo, A.I.; Pajares, M.; Rada, P.; Nuñez, A.; Nevado-Holgado, A.J.; Killik, R.; Van Leuven, F.; Ribe, E.; Lovestone, S.; Yamamoto, M.; Cuadrado, A. NRF2 deficiency replicates transcriptomic changes in Alzheimer’s patients and worsens APP and TAU pathology. Redox Biol., 2017, 13, 444-451.
Deponte, M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim. Biophys. Acta, 2013, 1830(5), 3217-3266.
Zhao, Y.; Seefeldt, T.; Chen, W.; Wang, X.; Matthees, D.; Hu, Y.; Guan, X. Effects of glutathione reductase inhibition on cellular thiol redox state and related systems. Arch. Biochem. Biophys., 2009, 485(1), 56-62.
Erden Inal, M.; Akgün, A.; Kahraman, A. The effects of exogenous glutathione on reduced glutathione level, glutathione peroxidase and glutathione reductase activities of rats with different ages and gender after whole-body Γ-irradiation. J. Am. Aging Assoc., 2003, 26(3-4), 55-58.
Zuzak, E.; Horecka, A.; Kiełczykowska, M.; Dudek, A.; Musik, I.; Kurzepa, J.; Kurzepa, J. Glutathione level and glutathione reductase activity in serum of coronary heart disease patients. J. Pre Clin. Clin. Res, 2017, 11(2), 103-105.
Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J. Med., 2018, 54(4), 287-293.
Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS sources in physiological and pathological conditions. Oxid. Med. Cell. Longev., 2016, 2016, 1245049.
Fu, Y.; Chung, F.L. Oxidative stress and hepatocarcinogenesis. Hepatoma Res., 2018, 4(8), 39.
Carini, F.; Mazzola, M.; Rappa, F.; Jurjus, A.; Geagea, A.G.; Al Kattar, S.; Bou-Assi, T.; Jurjus, R.; Damiani, P.; Leone, A.; Tomasello, G. Colorectal carcinogenesis: Role of oxidative stress and antioxidants. Anticancer Res., 2017, 37(9), 4759-4766.
Jezierska-Drutel, A.; Rosenzweig, S.A.; Neumann, C.A. Role of oxidative stress and the microenvironment in breast cancer development and progression. Adv. Cancer Res., 2013, 119, 107-125.
Wang, Z.; Li, Z.; Ye, Y.; Xie, L.; Li, W. Oxidative stress and liver cancer: Etiology and therapeutic targets. Oxid. Med. Cell. Longev., 2016, 2016, 10.
Yu, J.; Liu, F.; Yin, P.; Zhao, H.; Luan, W.; Hou, X.; Zhong, Y.; Jia, D.; Zan, J.; Ma, W.; Shu, B.; Xu, J. Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine. Stress, 2013, 16(1), 99-113.
Illam, S.P.; Narayanankutty, A.; Mathew, S.E.; Valsalakumari, R.; Jacob, R.M.; Raghavamenon, A.C. Epithelial mesenchymal transition in cancer progression: Prev entive phytochemicals. Recent Pat Anticancer Drug Discov., 2017, 12(3), 234-246.
Roy, N.; Davis, S.; Narayanankutty, A.; Nazeem, P.; Babu, T.; Abida, P.; Valsala, P.; Raghavamenon, A.C. Garlic phytocompounds possess anticancer activity by specifically targeting breast cancer biomarkers - An in silico study. Asian Pac. J. Cancer Prev., 2016, 17(6), 2883-2888.
Roy, N.; Narayanankutty, A.; Nazeem, P.A.; Valsalan, R.; Babu, T.D.; Mathew, D. Plant phenolics ferulic acid and P-coumaric acid inhibit colorectal cancer cell proliferation through EGFR down-regulation. Asian Pac. J. Cancer Prev., 2016, 17(8), 4019-4023.
Roy, N.; Nazeem, P.A.; Babu, T.D.; Abida, P.S.; Narayanankutty, A.; Valsalan, R.; Valsala, P.A.; Raghavamenon, A.C. EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide. Interdiscip. Sci., 2018, 10(4), 686-693.
Shweta, M.; Arunaksharan, N. Traditional fruits of Kerala: Bioactive compounds and their curative potential in chronic diseases. Curr. Nutr. Food Sci., 2017, 13(4), 279-289.
Niedzwiecki, A.; Roomi, M.W.; Kalinovsky, T.; Rath, M. Anticancer efficacy of polyphenols and their combinations. Nutrients, 2016, 8(9), E552.
Batra, P.; Sharma, A.K. Anti-cancer potential of flavonoids: Recent trends and future perspectives. 3 Biotech, 2013, 3(6), 439-459.
Kumar, H.; Kim, I.S.; More, S.V.; Kim, B.W.; Choi, D.K. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat. Prod. Rep., 2014, 31(1), 109-139.
Ngo, Q.M.; Tran, P.T.; Tran, M.H.; Kim, J.A.; Rho, S.S.; Lim, C.H.; Kim, J.C.; Woo, M.H.; Choi, J.S.; Lee, J.H.; Min, B.S. Alkaloids from Piper nigrum exhibit antiinflammatory activity via activating the Nrf2/HO-1 pathway. Phytother. Res., 2017, 31(4), 663-670.
Isah, T. Anticancer alkaloids from trees: Development into drugs. Pharmacogn. Rev., 2016, 10(20), 90-99.
Huang, M.; Lu, J.J.; Huang, M.Q.; Bao, J.L.; Chen, X.P.; Wang, Y.T. Terpenoids: Natural products for cancer therapy. Expert Opin. Investig. Drugs, 2012, 21(12), 1801-1818.
Lewandowska, H.; Kalinowska, M.; Lewandowski, W.; Stępkowski, T.M.; Brzóska, K. The role of natural polyphenols in cell signaling and cytoprotection against cancer development. J. Nutr. Biochem., 2016, 32, 1-19.
Hussain, T.; Tan, B.; Liu, G.; Murtaza, G.; Rahu, N.; Saleem, M.; Yin, Y. Modulatory mechanism of polyphenols and Nrf2 signaling pathway in LPS challenged pregnancy disorders. Oxid. Med. Cell. Longev., 2017, 2017, 8254289.
Pallauf, K.; Duckstein, N.; Hasler, M.; Klotz, L.O.; Rimbach, G. Flavonoids as putative inducers of the transcription factors Nrf2, FoxO, and PPARγ. Oxid. Med. Cell. Longev., 2017, 2017, 4397340.
Droge, W.; Breitkreutz, R. Glutathione and immune function. Proc. Nutr. Soc., 2000, 59(4), 595-600.
Harbrecht, B.G.; Di Silvio, M.; Chough, V.; Kim, Y.M.; Simmons, R.L.; Billiar, T.R. Glutathione regulates nitric oxide synthase in cultured hepatocytes. Annals. Surg., 1997, 225(1), 76-87.
Vahora, H.; Khan, M.A.; Alalami, U.; Hussain, A. The potential role of nitric oxide in halting cancer progression through chemoprevention. J. Cancer Prev., 2016, 21(1), 1-12.
Buchmuller-Rouiller, Y.; Corrandin, S.B.; Smith, J.; Schneider, P.; Ransijn, A.; Jongeneel, C.V.; Mauël, J. Role of glutathione in macrophage activation: Effect of cellular glutathione depletion on nitrite production and leishmanicidal activity. Cell. Immunol., 1995, 164(1), 73-80.
Mak, T.W.; Grusdat, M.; Duncan, G.S.; Dostert, C.; Nonnenmacher, Y.; Cox, M.; Binsfeld, C.; Hao, Z.; Brüstle, A.; Itsumi, M.; Jäger, C.; Chen, Y.; Pinkenburg, O.; Camara, B.; Ollert, M.; Bindslev-Jensen, C.; Vasiliou, V.; Gorrini, C.; Lang, P.A.; Lohoff, M.; Harris, I.S.; Hiller, K.; Brenner, D. Glutathione primes T cell metabolism for inflammation. Immunity, 2017, 46(4), 675-689.
Biswas, S.K.; McClure, D.; Jimenez, L.A.; Megson, I.L.; Rahman, I. Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: Mechanism of free radical scavenging activity. Antioxid. Redox Signal., 2005, 7(1-2), 32-41.
Mariyappan, P.; Kalaiyarasu, T.; Manju, V. Effect of eriodictyol on preneoplastic lesions, oxidative stress and bacterial enzymes in 1,2-dimethyl hydrazine-induced colon carcinogenesis. Toxicol. Res., 2017, 6(5), 678-692.
Sharma, S.H.; Chellappan, D.R.; Chinnaswamy, P.; Nagarajan, S. Protective effect of p-coumaric acid against 1,2 dimethylhydrazine induced colonic preneoplastic lesions in experimental rats. Biomed. Pharmacother., 2017, 94, 577-588.
Siddique, A.I.; Mani, V.; Arivalagan, S.; Thomas, N.S.; Namasivayam, N. Asiatic acid attenuates pre-neoplastic lesions, oxidative stress, biotransforming enzymes and histopathological alterations in 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis. Toxicol. Mech. Methods, 2017, 27(2), 136-150.
Siddique, A.I.; Mani, V.; Renganathan, S.; Ayyanar, R.; Nagappan, A.; Namasivayam, N. Asiatic acid abridges pre-neoplastic lesions, inflammation, cell proliferation and induces apoptosis in a rat model of colon carcinogenesis. Chem. Biol. Interact., 2017, 278, 197-211.
Vinothkumar, R.; Vinoth Kumar, R.; Sudha, M.; Viswanathan, P.; Balasubramanian, T.; Nalini, N. Modulatory effect of troxerutin on biotransforming enzymes and preneoplasic lesions induced by 1,2-dimethylhydrazine in rat colon carcinogenesis. Exp. Mol. Pathol., 2014, 96(1), 15-26.
Das, L.; Vinayak, M. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS One, 2015, 10(4), e0124000.
Amalraj, A.; Pius, A.; Gopi, S.; Gopi, S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review. J. Tradit. Complement. Med., 2017, 7(2), 205-233.
Sharma, R.A.; Ireson, C.R.; Verschoyle, R.D.; Hill, K.A.; Williams, M.L.; Leuratti, C.; Manson, M.M.; Marnett, L.J.; Steward, W.P.; Gescher, A. Effects of dietary curcumin on glutathione- S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa. Clin. Cancer Res., 2001, 7(5), 1452-1458.
Hussein, R.H.; Khalifa, F.K. The protective role of ellagitannins flavonoids pretreatment against N-nitrosodiethylamine induced-hepatocellular carcinoma. Saudi J. Biol. Sci., 2014, 21(6), 589-596.
Siddique, Y.H.; Ali, F. Protective effect of epigallocatechin gallate against N-nitrosodiethylamine (NDEA) induced toxicity in rats. Cogent Biol., 2016, 2(1), 1141451.
Ramakrishnan, G.; Raghavendran, H.R.; Vinodhkumar, R.; Devaki, T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem. Biol. Interact., 2006, 161(2), 104-114.
Hawk, M.A.; McCallister, C.; Schafer, Z.T. Antioxidant activity during tumor progression: A necessity for the survival of cancer cells? Cancers, 2016, 8(10), 92.
Davison, C.A.; Durbin, S.M.; Thau, M.R.; Zellmer, V.R.; Chapman, S.E.; Diener, J.; Wathen, C.; Leevy, W.M.; Schafer, Z.T. Antioxidant enzymes mediate survival of breast cancer cells deprived of extracellular matrix. Cancer Res., 2013, 73(12), 3704-3715.
Kamarajugadda, S.; Cai, Q.; Chen, H.; Nayak, S.; Zhu, J.; He, M.; Jin, Y.; Zhang, Y.; Ai, L.; Martin, S.S.; Tan, M.; Lu, J. Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis. Cell Death Dis., 2013, 21(4), 20.
Li, S.; Mao, Y.; Zhou, T.; Luo, C.; Xie, J.; Qi, W.; Yang, Z.; Ma, J.; Gao, G.; Yang, X. Manganese superoxide dismutase mediates anoikis resistance and tumor metastasis in nasopharyngeal carcinoma. Oncotarget, 2016, 7(22), 32408-32420.
Zhang, H.J.; Zhao, W.; Venkataraman, S.; Robbins, M.E.; Buettner, G.R.; Kregel, K.C.; Oberley, L.W. Activation of matrix metalloproteinase-2 by overexpression of manganese superoxide dismutase in human breast cancer MCF-7 cells involves reactive oxygen species. J. Biol. Chem., 2002, 277(23), 20919-20926.
Bansal, A.; Simon, M.C. Glutathione metabolism in cancer progression and treatment resistance. J. Cell Biol., 2018, 217(7), 2291-2298.
Rocha, C.R.R.; Garcia, C.C.M.; Vieira, D.B.; Quinet, A.; de Andrade-Lima, L.C.; Munford, V.; Belizário, J.E.; Menck, C.F. Glutathione depletion sensitizes cisplatin- and temozolomide-resistant glioma cells in vitro and in vivo. Cell Death Dis., 2014, 5, e1505.
Liebmann, J.E.; Hahn, S.M.; Cook, J.A.; Lipschultz, C.; Mitchell, J.B.; Kaufman, D.C. Glutathione depletion by L-buthionine sulfoximine antagonizes taxol cytotoxicity. Cancer Res., 1993, 53(9), 2066-2070.
Li, S.; Li, C.; Jin, S.; Liu, J.; Xue, X.; Eltahan, A.S.; Sun, J.; Tan, J.; Dong, J.; Liang, X.J. Overcoming resistance to cisplatin by inhibition of glutathione S-transferases (GSTs) with ethacraplatin micelles in vitro and in vivo. Biomaterials, 2017, 144, 119-129.
Saga, Y.; Ohwada, M.; Suzuki, M.; Konno, R.; Kigawa, J.; Ueno, S.; Mano, H. Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma. Oncol. Rep., 2008, 20(6), 1299-1303.
Ramachandran, C.; Yuan, Z.K.; Huang, X.L.; Krishan, A. Doxorubicin resistance in human melanoma cells: MDR-1 and glutathione S-transferase pi gene expression. Biochem. Pharmacol., 1993, 45(3), 743-751.
Wang, K.; Ramji, S.; Bhathena, A.; Lee, C.; Riddick, D.S. Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines. Xenobiotica, 1999, 29(2), 155-170.
Zhu, Z.; Du, S.; Du, Y.; Ren, J.; Ying, G.; Yan, Z. Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis. J. Neurochem., 2018, 144(1), 93-104.
Lo, H.W.; Ali-Osman, F. Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr. Opin. Pharmacol., 2007, 7(4), 367-374.
Wu, S.; Wang, Y.J.; Tang, X.; Wang, Y.; Wu, J.; Ji, G.; Zhang, M.; Chen, G.; Liu, Q.; Sandford, A.J.; He, J.Q. Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the incidence of anti-tuberculosis drug-induced hepatotoxicity. PLoS One, 2016, 11(6), e0157478.
Townsend, D.M.; Tew, K.D. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 2002, 22, 7369.
Wongtrakul, J.; Sukittikul, S.; Saisawang, C.; Ketterman, A.J. Mitogen-activated protein kinase p38b interaction with delta class glutathione transferases from the fruit fly, Drosophila melanogaster. J. Insect Sci., 2012, 12, 107-107.
Kang, K.W.; Ryu, J.H.; Kim, S.G. The essential role of phosphatidylinositol 3-kinase and of p38 mitogen-activated protein kinase activation in the antioxidant response element-mediated rGSTA2 induction by decreased glutathione in H4IIE hepatoma cells. Mol. Pharmacol., 2000, 58(5), 1017-1025.
Samuels, B.L.; Murray, J.L.; Cohen, M.B.; Safa, A.R.; Sinha, B.K.; Townsend, A.J.; Beckett, M.A.; Weichselbaum, R.R. Increased glutathione peroxidase activity in a human sarcoma cell line with inherent doxorubicin resistance. Cancer Res., 1991, 51(2), 521-527.
Peters, W.H.; Roelofs, H.M. Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco-2 human colon adenocarcinoma cells: A possible role for glutathione S-transferases. Cancer Res., 1992, 52(7), 1886-1890.
Beaumont, P.O.; Moore, M.J.; Ahmad, K.; Payne, M.M.; Lee, C.; Riddick, D.S. Role of glutathione S-transferases in the resistance of human colon cancer cell lines to doxorubicin. Cancer Res., 1998, 58(5), 947-955.
Mulder, T.P.; Manni, J.J.; Roelofs, H.M.; Peters, W.H.; Wiersma, A. Glutathione S-transferases and glutathione in human head and neck cancer. Carcinogenesis, 1995, 16(3), 619-624.
Marklund, S.L.; Westman, N.G.; Roos, G.; Carlsson, J. Radiation resistance and the CuZn superoxide dismutase, Mn superoxide dismutase, catalase, and glutathione peroxidase activities of seven human cell lines. Radiat. Res., 1984, 100(1), 115-123.
Hall, M.D.; Marshall, T.S.; Kwit, A.D.T.; Miller Jenkins, L.M.; Dulcey, A.E.; Madigan, J.P.; Pluchino, K.M.; Goldsborough, A.S.; Brimacombe, K.R.; Griffiths, G.L.; Gottesman, M.M. Inhibition of glutathione peroxidase mediates the collateral sensitivity of multidrug-resistant cells to tiopronin. J. Biol. Chem., 2014, 289(31), 21473-21489.
Bernig, T.; Ritz, S.; Brodt, G.; Volkmer, I.; Staege, M.S. Glutathione-S-transferases and chemotherapy resistance of Hodgkin’s lymphoma cell lines. Anticancer Res., 2016, 36(8), 3905-3915.
Chen, H.H.W.; Kuo, M.T. Role of glutathione in the regulation of Cisplatin resistance in cancer chemotherapy. Met. Based Drugs, 2010, 2010, 430939.
Meijer, C.; Mulder, N.H.; Hospers, G.A.; Uges, D.R. de Vries, E.G. The role of glutathione in resistance to cisplatin in a human small cell lung cancer cell line. Br. J. Cancer, 1990, 62(1), 72-77.
Azmi, A.S.; Sarkar, F.H.; Hadi, S.M. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property. F1000 Res., 2013, 2, 135.
Yu, M.; Liu, Y.; Duan, Y.; Chen, Y.; Han, J.; Sun, L. Yang. X. Inhibition of glutathione production by L-S,R-buthionine sulfoximine activates hepatic ascorbate synthesis - A unique anti-oxidative stress mechanism in mice. Biochem. Biophys. Res. Commun., 2017, 484(1), 56-63.
Du, M.; Zhang, L.; Scorsone, K.A.; Woodfield, S.E.; Zage, P.E. Nifurtimox is effective against neural tumor cells and is synergistic with buthionine sulfoximine. Sci. Rep., 2016, 6, 27458.
Schnelldorfer, T.; Gansauge, S.; Gansauge, F.; Schlosser, S.; Beger, H.G.; Nussler, A.K. Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer, 2000, 89(7), 1440-1447.
Lewis-Wambi, J.S.; Kim, H.R.; Wambi, C.; Patel, R.; Pyle, J.R.; Klein-Szanto, A.J.; Jordan, V.C. Buthionine sulfoximine sensitizes antihormone-resistant human breast cancer cells to estrogen-induced apoptosis. Breast Cancer Res., 2008, 10(6), R104.
Lee, M.; Jo, A.; Lee, S.; Kim, J.B.; Chang, Y.; Nam, J.Y.; Cho, H.; Cho, Y.Y.; Cho, E.J.; Lee, J.H.; Yu, S.J.; Yoon, J.H.; Kim, Y.J. 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. PLoS One, 2017, 12(3), e0174271.
Anderson, C.P.; Keshelava, N.; Satake, N.; Meek, W.H.; Reynolds, C.P. Synergism of buthionine sulfoximine and melphalan against neuroblastoma cell lines derived after disease progression. Med. Pediatr. Oncol., 2000, 35(6), 659-662.
Faundez, M.; Pino, L.; Letelier, P.; Ortiz, C.; López, R.; Seguel, C.; Ferreira, J.; Pavani, M.; Morello, A.; Maya, J.D. Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. Antimicrob. Agents Chemother., 2005, 49(1), 126-130.
Tagde, A.; Singh, H.; Kang, M.H.; Reynolds, C.P. The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma. Blood Cancer J., 2014, 4, e229.
Anderson, C.P.; Reynolds, C.P. Synergistic cytotoxicity of buthionine sulfoximine (BSO) and intensive melphalan (L-PAM) for neuroblastoma cell lines established at relapse after myeloablative therapy. Bone Marrow Transplant., 2002, 30(3), 135-140.
Garbutcheon-Singh, K.B.; Harper, B.W.; Myers, S.; Aldrich-Wright, J.R. Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin. Metallomics, 2014, 6(1), 126-131.
Port, J.L.; Hochwald, S.N.; Wang, H.Y.; Burt, M.E. Buthionine sulfoximine pretreatment potentiates the effect of isolated lung perfusion with doxorubicin. Ann. Thorac. Surg., 1995, 60(2), 239-243.
Imamura, M.; Seki, T.; Kunieda, K.; Wakabayashi, M.; Inoue, K.; Obiya, Y.; Harada, K. Antitumor effects of Doxorubicin hydrochloride (dox) and buthionine sulfoximine (bso)-hydroxyapatite (hap) complex on transplanted tumors in-vivo. Oncol. Rep., 1995, 2(4), 509-511.
Mustafa, E.H.; Mahmoud, H.T.; Al-Hudhud, M.Y.; Abdalla, M.Y.; Ahmad, I.M.; Yasin, S.R.; Elkarmi, A.Z.; Tahtamouni, L.H. 2-deoxy-D-glucose synergizes with doxorubicin or L-buthionine sulfoximine to reduce adhesion and migration of breast cancer cells. Asian Pac. J. Cancer Prev., 2015, 16(8), 3213-3222.
Liu, B.; Huang, X.; Hu, Y.; Chen, T.; Peng, B.; Gao, N.; Jin, Z.; Jia, T.; Zhang, N.; Wang, Z.; Jin, G. Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer. Oncotarget, 2016, 7(36), 58038-58050.
Lu, D.; Liu, J.X.; Endo, T.; Zhou, H.; Yao, S.; Willert, K.; Schmidt-Wolf, I.G.; Kipps, T.J.; Carson, D.A. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the wnt/β-catenin pathway. PLoS One, 2009, 4(12), e8294.
Lee, E.; Reed, G.; Dandawate, P.; Kaushik, G.; Subramaniam, D.; Holzbeierlein, J.M.; Anant, S.; Weir, S.J. Repurposing ethacrynic acid for the treatment of bladder cancer. J. Clin. Oncol., 2018, 36(6)(Suppl.), 521.
Rhodes, T.; Twentyman, P.R. A study of ethacrynic acid as a potential modifier of melphalan and cisplatin sensitivity in human lung cancer parental and drug-resistant cell lines. Br. J. Cancer, 1992, 65(5), 684-690.
Wang, J.; Seebacher, N.; Shi, H.; Kan, Q.; Duan, Z. Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget, 2017, 8(48), 84559-84571.
Radenkovic, F.; Holland, O.; Vanderlelie, J.J.; Perkins, A.V. Selective inhibition of endogenous antioxidants with Auranofin causes mitochondrial oxidative stress which can be countered by selenium supplementation. Biochem. Pharmacol., 2017, 146, 42-52.
Roder, C.; Thomson, M.J. Auranofin: Repurposing an old drug for a golden new age. Drugs, 2015, 15(1), 13-20.
You, B.R.; Park, W.H. Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion. Oncol. Rep., 2016, 35(1), 546-551.
Li, H.; Hu, J.; Wu, S.; Wang, L.; Cao, X.; Zhang, X.; Dai, B.; Cao, M.; Shao, R.; Zhang, R.; Majidi, M.; Ji, L.; Heymach, J.V.; Wang, M.; Pan, S.; Minna, J.; Mehran, R.J.; Swisher, S.G.; Roth, J.A.; Fang, B. Auranofin-mediated inhibition of PI3K/AKT/mTOR axis and anticancer activity in non-small cell lung cancer cells. Oncotarget, 2015, 7(3), 3548-3558.
Hu, J.; Zhang, H.; Cao, M.; Wang, L.; Wu, S.; Fang, B. Auranofin enhances Ibrutinib’s anticancer activity in EGFR-mutant lung adenocarcinoma. Mol. Cancer Ther., 2018, 17(10), 2156-2163.
Park, S.H.; Lee, J.H.; Berek, J.S.; Hu, M.C. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int. J. Oncol., 2014, 45(4), 1691-1698.
Vahrmeijer, A.L.; van Dierendonck, J.H.; Schutrups, J.; van de Velde, C.J.; Mulder, G.J. Effect of glutathione depletion on inhibition of cell cycle progression and induction of apoptosis by melphalan (L-phenylalanine mustard) in human colorectal cancer cells. Biochem. Pharmacol., 1999, 58(4), 655-664.
Li, Q.; Yin, X.; Wang, W.; Zhan, M.; Zhao, B.; Hou, Z.; Wang, J. The effects of buthionine sulfoximine on the proliferation and apoptosis of biliary tract cancer cells induced by cisplatin and gemcitabine. Oncol. Lett., 2016, 11(1), 474-480.
Lewis-Wambi, J.; Kim, H.; Wambi, C.; Jordan, V.C. Glutathione depletion sensitizes hormone-independent human breast cancer cells to estrogen-induced apoptosis. Cancer Res., 2008, 68((9 Supplement)), 2687.
You, B.R.; Shin, H.R.; Han, B.R.; Kim, S.H.; Park, W.H. Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion. Mol. Med. Rep., 2015, 11(2), 1428-1434.
Park, W.H. Gallic acid induces HeLa cell death via increasing GSH depletion rather than ROS levels. Oncol. Rep., 2017, 37(2), 1277-1283.
You, B.R.; Park, W.H. Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2 and oxidative stress-dependent manner. Int. J. Oncol., 2013, 42(1), 359-366.
Jaudan, A.; Sharma, S.; Malek, S.N.A.; Dixit, A. Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action. PLoS One, 2018, 13(2), e0191523.
Kim, E.H.; Baek, S.; Shin, D.; Lee, J.; Roh, J.L. Hederagenin induces apoptosis in cisplatin-resistant head and neck cancer cells by inhibiting the Nrf2-ARE antioxidant pathway. Oxid. Med. Cell. Longev., 2017, 2017, 12.
Sivakumaran, N.; Samarakoon, S.R.; Adhikari, A.; Ediriweera, M.K.; Tennekoon, K.H.; Malavige, N.; Thabrew, I.; Shrestha, R.L.S. Cytotoxic and apoptotic effects of govaniadine isolated from corydalis govaniana wall. Roots on human breast cancer (MCF-7) cells. BioMed Res. Int., 2018, 2018, 3171348.
Deeb, D.; Gao, X.; Liu, Y.B.; Gautam, S.C. Inhibition of cell proliferation and induction of apoptosis by CDDO-Me in pancreatic cancer cells is ROS-dependent. J. Exp. Therap. Oncol., 2012, 10(1), 51-64.
Brautigam, M.; Teusch, N.; Schenk, T.; Sheikh, M.; Aricioglu, R.Z.; Borowski, S.H.; Neudörfl, J.M.; Baumann, U.; Griesbeck, A.G.; Pietsch, M. Selective inhibitors of glutathione transferase P1 with trioxane structure as anticancer agents. ChemMedChem, 2015, 10(4), 629-639.
Chen, C.; Wu, C.; Lu, X.; Yan, Z.; Gao, J.; Zhao, H.; Li, S. Coniferyl ferulate, a strong inhibitor of glutathione s-transferase isolated from radix angelicae sinensis, reverses multidrug resistance and downregulates P-glycoprotein. Evid. Based Complement. Alternat. Med., 2013, 2013, 639083.
Ruzza, P.; Calderan, A. Glutathione Transferase (GST)-activated prodrugs. Pharmaceutics, 2013, 5(2), 220-231.
Ramsay, E.E.; Dilda, P.J. Glutathione S-conjugates as prodrugs to target drug-resistant tumors. Front. Pharmacol., 2014, 5, 181.
Dourado, D.F.; Fernandes, P.A.; Ramos, M.J.; Mannervik, B. Mechanism of glutathione transferase P1-1-catalyzed activation of the prodrug canfosfamide (TLK286, TELCYTA). Biochemistry, 2013, 52(45), 8069-8078.
Tew, K.D. TLK-286: A novel glutathione S-transferase-activated prodrug. Expert Opin. Investig. Drugs, 2005, 14(8), 1047-1054.
Rosen, L.S.; Brown, J.; Laxa, B.; Boulos, L.; Reiswig, L.; Henner, W.D.; Lum, R.T.; Schow, S.R.; Maack, C.A.; Keck, J.G.; Mascavage, J.C.; Dombroski, J.A.; Gomez, R.F.; Brown, G.L. Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies. Clin. Cancer Res., 2003, 9(5), 1628-1638.
Rosen, L.S.; Laxa, B.; Boulos, L.; Wiggins, L.; Keck, J.G.; Jameson, A.J.; Parra, R.; Patel, K.; Brown, G.L. Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies. Clin. Cancer Res., 2004, 10(11), 3689-3698.
Sequist, L.V.; Fidias, P.M.; Temel, J.S.; Kolevska, T.; Rabin, M.S.; Boccia, R.V.; Burris, H.A.; Belt, R.J.; Huberman, M.S.; Melnyk, O.; Mills, G.M.; Englund, C.W.; Caldwell, D.C.; Keck, J.G.; Meng, L.; Jones, M.; Brown, G.L.; Edelman, M.J.; Lynch, T.J. Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer. J. Thorac. Oncol., 2009, 4(11), 1389-1396.
Vergote, I.; Finkler, N.; del Campo, J.; Lohr, A.; Hunter, J.; Matei, D.; Kavanagh, J.; Vermorken, J.B.; Meng, L.; Jones, M.; Brown, G.; Kaye, S. ASSIST-1 Study Group. Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. Eur. J. Cancer, 2009, 45(13), 2324-2332.
Kavanagh, J.J.; Gershenson, D.M.; Choi, H.; Lewis, L.; Patel, K.; Brown, G.L.; Garcia, A.; Spriggs, D.R. Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Int. J. Gynecol. Cancer, 2005, 15(4), 593-600.
Vergote, I.; Finkler, N.J.; Hall, J.B.; Melnyk, O.; Edwards, R.P.; Jones, M.; Keck, J.G.; Meng, L.; Brown, G.L.; Rankin, E.M.; Burke, J.J.; Boccia, R.V.; Runowicz, C.D.; Rose, P.G. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int. J. Gynecol. Cancer, 2010, 20(5), 772-780.
Kavanagh, J.J.; Levenback, C.F.; Ramirez, P.T.; Wolf, J.L.; Moore, C.L.; Jones, M.R.; Meng, L.; Brown, G.L.; Bast, R.C. Jr. Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer. J. Hematol. Oncol., 2010, 3(9), 1756-8722.
Rojas, L.B.; Gomes, M.B. Metformin: An old but still the best treatment for type 2 diabetes. Diabetol. Metab. Syndr., 2013, 5(1), 1758-5996.
Rautio, J.; Vernerova, M.; Aufderhaar, I.; Huttunen, K.M. Glutathione-S-transferase selective release of metformin from its sulfonamide prodrug. Bioorg. Med. Chem. Lett., 2014, 24(21), 5034-5036.
Huerta, S. Nitric oxide for cancer therapy. Future Sci., 2015, 1(1), FSO44.
Luanpitpong, S.; Chanvorachote, P. Nitric oxide and aggressive behavior of lung cancer cells. Anticancer Res., 2015, 35(9), 4585-4592.
Xu, W.; Liu, L.Z.; Loizidou, M.; Ahmed, M.; Charles, I.G. The role of nitric oxide in cancer. Cell Res., 2002, 12(5-6), 311-320.
Chakrapani, H.; Kalathur, R.C.; Maciag, A.E.; Citro, M.L.; Ji, X.; Keefer, L.K.; Saavedra, J.E. Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs. Bioorg. Med. Chem., 2008, 16(22), 9764-9771.
Xue, R.; Wu, J.; Luo, X.; Gong, Y.; Huang, Y.; Shen, X.; Zhang, H.; Zhang, Y.; Huang, Z. Design, synthesis, and evaluation of diazeniumdiolate-based dna cross-linking agents activatable by glutathione S-transferase. Org. Lett., 2016. [Epub ahead of print].
Liu, J.; Li, C.; Qu, W.; Leslie, E.; Bonifant, C.L.; Buzard, G.S.; Saavedra, J.E.; Keefer, L.K.; Waalkes, M.P. Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol. Cancer Ther., 2004, 3(6), 709-714.
Maciag, A.E.; Holland, R.J.; Robert Cheng, Y.S.; Rodriguez, L.G.; Saavedra, J.E.; Anderson, L.M.; Keefer, L.K. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance. Redox Biol., 2013, 1(1), 115-124.
Maciag, A.E.; Chakrapani, H.; Saavedra, J.E.; Morris, N.L.; Holland, R.J.; Kosak, K.M.; Shami, P.J.; Anderson, L.M.; Keefer, L.K. The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: Involvement of reactive oxygen species. J. Pharmacol. Exp. Ther., 2011, 336(2), 313-320.
Tan, G.; Qiu, M.; Chen, L.; Zhang, S.; Ke, L.; Liu, J.J.S-K. a nitric oxide pro-drug, regulates growth and apoptosis through the ubiquitin-proteasome pathway in prostate cancer cells. BMC Cancer, 2017, 17(1), 376.
Edes, K.; Cassidy, P.; Shami, P.J.; Moos, P.J.J.S-K. a nitric oxide prodrug, has enhanced cytotoxicity in colon cancer cells with knockdown of thioredoxin reductase 1. PLoS One, 2010, 5(1), e8786.
Dong, R.; Wang, X.; Wang, H.; Liu, Z.; Liu, J.; Saavedra, J.E. Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells. Biomed. Pharmacother., 2017, 88, 367-373.
Simeone, A.M.; McMurtry, V.; Nieves-Alicea, R.; Saavedra, J.E.; Keefer, L.K.; Johnson, M.M.; Tari, A.M. TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells. Breast Cancer Res., 2008, 10(3), R44.
Shafei, A.; El-Bakly, W.; Sobhy, A.; Wagdy, O.; Reda, A.; Aboelenin, O.; Marzouk, A.; El Habak, K.; Mostafa, R.; Ali, M.A.; Ellithy, M. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed. Pharmacother., 2017, 95, 1209-1218.
Kepinska, M.; Kizek, R.; Milnerowicz, H. Fullerene as a doxorubicin nanotransporter for targeted breast cancer therapy: Capillary electrophoresis analysis. Electrophoresis, 2018, 39(18), 2370-2379.
Cox, J.; Weinman, S. Mechanisms of doxorubicin resistance in hepatocellular carcinoma. Hepatic. Oncol., 2016, 3(1), 57-59.
Lovitt, C.J.; Shelper, T.B.; Avery, V.M. Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins. BMC Cancer, 2018, 18(1), 41.
Johansson, K.; Ito, M.; Schophuizen, C.M.; Mathew Thengumtharayil, S.; Heuser, V.D.; Zhang, J.; Shimoji, M.; Vahter, M.; Ang, W.H.; Dyson, P.J.; Shibata, A.; Shuto, S.; Ito, Y.; Abe, H.; Morgenstern, R. Characterization of new potential anticancer drugs designed to overcome glutathione transferase mediated resistance. Mol. Pharm., 2011, 8(5), 1698-1708.
van Gisbergen, M.W.; Cebula, M.; Zhang, J.; Ottosson-Wadlund, A.; Dubois, L.; Lambin, P.; Tew, K.D.; Townsend, D.M.; Haenen, G.R.; Drittij-Reijnders, M.J.; Saneyoshi, H.; Araki, M.; Shishido, Y.; Ito, Y.; Arnér, E.S.; Abe, H.; Morgenstern, R.; Johansson, K. Chemical reactivity window determines prodrug efficiency toward glutathione transferase overexpressing cancer cells. Mol. Pharm., 2016, 13(6), 2010-2025.
Carroll, R.E.; Benya, R.V.; Turgeon, D.K.; Vareed, S.; Neuman, M.; Rodriguez, L.; Kakarala, M.; Carpenter, P.M.; McLaren, C.; Meyskens, F.L. Jr, Brenner, D.E. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. (Phila.), 2011, 4(3), 354-364.
Alumkal, J.J.; Slottke, R.; Schwartzman, J.; Cherala, G.; Munar, M.; Graff, J.N.; Beer, T.M.; Ryan, C.W.; Koop, D.R.; Gibbs, A.; Gao, L.; Flamiatos, J.F.; Tucker, E.; Kleinschmidt, R.; Mori, M. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest. New Drugs, 2015, 33(2), 480-489.
Berman, A.Y.; Motechin, R.A.; Wiesenfeld, M.Y.; Holz, M.K. The therapeutic potential of resveratrol: A review of clinical trials. NPJ Precis. Oncol., 2017, 1, 35.
Wang, J.; Xiong, T.; Zhou, J.; He, H.; Wu, D.; Du, X.; Li, X.; Xu, B. Enzymatic formation of curcumin in vitro and in vivo. Nano Res., 2018, 11(6), 3453-3461.
Baell, J.B.; Holloway, G.A. New substructure filters for removal of Pan Assay Interference Compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem., 2010, 53(7), 2719-2740.
Baell, J.B. Feeling nature’s PAINS: Natural products, natural product drugs, and Pan Assay Interference Compounds (PAINS). J. Nat. Prod., 2016, 79(3), 616-628.
Bhatia, M.; McGrath, K.L.; Di Trapani, G.; Charoentong, P.; Shah, F.; King, M.M.; Clarke, F.M.; Tonissen, K.F. The thioredoxin system in breast cancer cell invasion and migration. Redox Biol., 2015, 8, 68-78.
Tsuji, P.A.; Carlson, B.A.; Yoo, M.H.; Naranjo-Suarez, S.; Xu, X.M.; He, Y.; Asaki, E.; Seifried, H.E.; Reinhold, W.C.; Davis, C.D.; Gladyshev, V.N.; Hatfield, D.L. The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways. PLoS One, 2015, 10(4), e0124487.
Harris, I.S.; Treloar, A.E.; Inoue, S.; Sasaki, M.; Gorrini, C.; Lee, K.C.; Yung, K.Y.; Brenner, D.; Knobbe-Thomsen, C.B.; Cox, M.A.; Elia, A.; Berger, T.; Cescon, D.W.; Adeoye, A.; Brüstle, A.; Molyneux, S.D.; Mason, J.M.; Li, W.Y.; Yamamoto, K.; Wakeham, A.; Berman, H.K.; Khokha, R.; Done, S.J.; Kavanagh, T.J.; Lam, C.W.; Mak, T.W. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell, 2015, 27(2), 211-222.
Benhar, M.; Shytaj, I.L.; Stamler, J.S.; Savarino, A. Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. J. Clin. Investig., 2016, 126(5), 1630-1639.
Zhang, J.; Li, X.; Han, X.; Liu, R.; Fang, J. Targeting the thioredoxin system for cancer therapy. Trends Pharmacol. Sci., 2017, 38(9), 794-808.

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