Abstract
Calcitriol, the hormonal form of vitamin D, enhances the anticancer activity of the immune cytokine tumor necrosis factor, interleukin 1 and interleukin 6 in human breast and renal cell carcinoma cells without affecting the cytotoxic action of interferon-α or killer lymphocytes. It also enhances cytotoxicity induced by the anticancer drug doxorubicin, by the redox cycling quinone menadione, and by the reactive oxygen species hydrogen peroxide. The synergistic interaction was accompanied by increased oxidative stress, as manifested by glutathione depletion and was abolished by exposure to the thiol antioxidant N-acetylcysteine. The hormone on its own brought about an increase in the cellular redox state as reflected in the ratio between oxidized and reduced glutathione and glyceraldehyde-3-phosphate dehydrogenase, and a reduction in the expression of the antioxidant enzyme Cu/Zn superoxide dismutase These results support the notion that the interplay between active vitamin Dderivatives and other anticancer agents such as immune cytokines and anticancer drugs plays a role in the in vivo anticancer activity of vitamin D and that reactive oxygen species are involved in the anticancer activity of vitamin D on its own and in its cross-talk with other anticancer modalities.
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Broekemeier KM, KlocekeCK, Pfeiffer DR (1998) Proton selective substate of the mitochondrial permeability transition pore: regulation by the redox state of the electron transport chain. Biochemistry 37:13059–13065
Cho YL, Christensen C, Saunders DE, Lawrence WD, Deppe G, Malviya VK, Malone JM (1991) Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells. Cancer Res 51:2848–2853
Colston KW, Hansen CM (2002) Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 9:45–59
Denu JM, Tanner KG (1998) Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37:5633–5642
Doroshow JH, Akman S, Esworthy S, Chu FF, Burke T (1991) Doxorubicin resistance conferred by selective enhancement of intracellular glutathione peroxidase or superoxide dismutase content in human MCF-7 breast cancer cells. Free Radic Res Commun 12–13:779–781
Gewirtz DA (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57:727–741
Goossens V, De Vos K, Vercammen D, Steemans M, Vancompernolle K, Fiers W, Vandenabeele P, Grooten J (1999) Redox regulation of TNF signaling. Biofactors 10:145–156
Guyton KZ, Kensler TW, Posner GH (2001) Cancer chemoprevention using natural vitamin D and synthetic analogs. Annu Rev Pharmacol Toxicol 41:421–442
Koren R, Rocker D, Kotestiano O, Liberman UA, Ravid A (2000) Synergistic anticancer activity of 1,25-dihydroxyvitamin D3 and immune cytokines: the involvement of reactive oxygen species. J Steroid Biochem Mol Biol 73:105–112
Koren R, Hadari-Naor I, Zuck E, Rotem C, Liberman UA, Ravid A (2001) Vitamin D is a prooxidant in breast cancer cells. Cancer Res 61:1439–1444
Kuninaka S, Ichinose Y, Koja K, Toh Y (2000) Suppression of manganese superoxide dismutase augments sensitivity to radiation, hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis. Br J Cancer 83:928–934
Li JJ, Oberley LW (1997) Overexpression of manganese-containing superoxide dismutase confers resistance to the cytotoxicity of tumor necrosis factor alpha and/or hyperthermia. Cancer Res 57:1991–1998
Manna SK, Zhang HJ, Yan T, Oberley LW, Aggarwal BB (1998) Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J Biol Chem 273:13245–13254
Meier B, Radeke HH, Selle S, Younes M, Sies H, Resch K, Habermehl GG (1989) Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J 263:539–545
Meplan C, Richard MJ, Hainaut P (2000) Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59:25–33
Minotti G (1993) Sources and role of iron in lipid peroxidation. Chem Res Toxicol 6:134–146
Miyajima A, Nakashima J, Yoshioka K, Tachibana M, Tazaki H, Murai M (1997) Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells. Br J Cancer 76:206–210
Nakamura H, Nakamura K, Yodoi J (1997) Redox regulation of cellular activation. Annu Rev Immunol 15:351–369
Ngo EO, Sun TP, Chang JY, Wang CC, Chi KH, Cheng AL, Nutter LM (1991) Menadione-induced DNA damage in a human tumor cell line. Biochem Pharmacol 42:1961–1968
Nussler A, Drapier JC, Renia L, Pied S, Miltgen F, Gentilini M, Mazier D (1991) L-argininedependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur J Immunol 21:227–230
Obrador E, Carretero J, Pellicer JA, Estrela JM (2001) Possible mechanisms for tumour cell sensitivity to TNF-alpha and potential therapeutic applications. Curr Pharm Biotechnol 2:119–130
Ravid A, Rocker D, Machlenkin A, Rotem C, Hochman A, Kessler-Icekson G, Liberman UA, Koren R (1999) 1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. Cancer Res 59:862–867
Reichrath J (2001) Will analogs of 1,25-dihydroxyvitamin D3 (calcitriol) open a new era in cancer therapy? Onkologie 24:128–133
Rocker D, Ravid A, Liberman UA, Garach-Jehoshua O, Koren R (1994) 1,25-Dihydroxyvitamin D3 potentiates the cytotoxic effect of TNF on human breast cancer cells. Mol Cell Endocrinol 106:157–162
Sen CK, Packer L (1996) Antioxidant and redox regulation of gene transcription. FASEB J 10:709–720
Studzinski GP, Moore DC (1995) Sunlight can it prevent as well as cause cancer? Cancer Res 55:4014–4022
Sundaram S, Gewirtz DA (1999) The vitamin D3 analog EB 1089 enhances the response of human breast tumor cells to radiation. Radiat Res 152:479–486
Varbiro G, Veres B, Gallyas F Jr, Sumegi B (2001) Direct effect of Taxol on free radical formation and mitochondrial permeability transition. Free Radic Biol Med 31:548–558
Wang Q, Yang W, Uytingco MS, Christakos S, Wieder R (2000) 1,25-Dihydroxyvitamin D3 and all-trans-retinoic acid sensitize breast cancer cells to chemotherapy-induced cell death. Cancer Res 60:2040–2048
Yacobi R, Koren R, Liberman UA, Rotem C, Wasserman L, Ravid A (1996) 1,25-dihydroxyvitamin D3 increases the sensitivity of human renal carcinoma cells to tumor necrosis factor alpha but not to interferon alpha or lymphokine-activated killer cells. J Endocrinol 149:327–333
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Ravid, A., Koren, R. (2003). The Role of Reactive Oxygen Species in the Anticancer Activity of Vitamin D. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_26
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DOI: https://doi.org/10.1007/978-3-642-55580-0_26
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