TY - JOUR TT - Evaluation of the Effect on the Cell Cytotoxicity of Warfarin in K562 Leukemia Cell Line AU - Şencan, Sevide AU - Onaran, İlhan AU - Demirtaş, Halil PY - 2007 DA - March JF - Sağlık Bilimleri Dergisi JO - JHS PB - Erciyes University WT - DergiPark SN - 1018-3655 SP - 11 EP - 17 VL - 16 IS - 1 KW - Warfarin KW - K562 KW - kanser KW - sitotoksite KW - serbest radikal N2 - In the experimental studies of clinical and animal models, it has been reported that anticoagulants have prevented development of primary tumors and metastasis indirectly. It has been shown that warfarin (which is a well- known oral anticoagulant) have a cytotoxic effect on malignant cells, sparing normal cells. It has been suggested that this cytotoxic effect may be due to reactive oxygen species as superoxide and hydrogen peroxide produced in the malignant cells by warfarin, which is a potent electron transferring substance. However, this view is not encountered in literature. This study examined the oxidative and apoptotic potentials of warfarin on three cell types in vitro, namely, human chronic myelogenous leukemic K562 cells, promyelocytic leukemic HL-60 cells, and normal human peripheral blood mononuclear cells. The effects of warfarin were also compared with acetylsalicylic acid (ASA). The cells were incubated with 0-200 µM concentrations of warfarin and 100 µM ASA for 72 h at 37oC. The luminol and lucigenin-dependent chemiluminescense assay and 2', 7'-dichlorofluorescin diacetate (DCFH-DA) method were used as biomarkers of oxidative stress. Statistical analysis of data was performed by analysis of variance (ANOVA) and p<0.05 was considered statistically significant for all experiments. The present results indicate that the warfarin at the pharmacological concentrations (<50µM) have no prooxidant on K562 cells and HL-60 cells. However, DCFH oxidation was increased when cells were incubated with high concentrations (50-200 µM) of warfarin. On the other hand, our study suggests that oxidative stress does not seem to be involved in warfarin-induced DCFH of both cell lines. Therefore, the specific source(s) responsible to DCFH oxidation in leukemic cells in response to in vitro warfarin require future studies CR - Fuster V, Wayne AR, O’Rourke R. The Heart. Cilt 3 2004, pp 1411 CR - Ngui JS, Chen Q, Shou M, Wang RW, Stearns RA, Baillie TA, Tang W. In Vitro Stimulation of Warfarin Metabolism by Quinidine: Increases in the Formation of 4*- and 10- Hydroxywarfarin. Drug Metab Dispos 2001, 29(6): 877-886 CR - Bobek V, Kovarik J. Antitumor and antimetastatic effect of warfarin and heparins. Biomed Pharmacother 2004, 58: 213–219 CR - Zacharski LR, Prandomi P, Monreal M. Warfarin versus low-molecular weight haparin therapy in cancer. Oncologist 2005, 10(1): 72-79 CR - Berkarda B, Arda O, Tasyurekli M, Derman U. Mitochondrial-lytic action of warfarin in lymphocytes. Int J Clin Pharmacol Ther Toxicol 1992, 30(8): 277-279 CR - Dias N, Bailly C. Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol 2005, 70: 1–12 CR - Kınnula VL, Crapo JD. Superoxide dismutases in malignant cells and human tumors. Free Radic Biol Med 2004, 36(6): 718-744 CR - Cam Sımsek F, Yuksel M, Turker L, Haklar K, G ve ark. The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment. Int J Androl 2004, 27: 228–33 CR - Ohashi T, Mizutani A, Murakami A, Kojo S, Ishii T, Taketani S. Rapid oxidation of dichlorodihydro£uorescin with heme and hemoproteins: formation of the £uorescein is independent of the generation of reactive oxygen species. FEBS Lett 2002, 511: 21-27 CR - Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer 2002, 9: 1-9 CR - Muller-Hocker J, Aust D, Rohrbach H, Napiwotzky J, Reith A, Link TA, Seibel R, Holzel D, Kadenbach B. Defects of the Respiratory Chain in the Normal Human Liver and in Cirrhosis During Aging. Hepatology 1997, 26(3): 709-719 CR - Lawrence A, et al. Evidence for the role of a peroxidase compound I-type intermediate in the oxidation of glutathione, NADH, ascorbate and dichlorofluorescin by cytochrome c/H2O2 Implications for oxidative stress during apoptosis. J Biol Chem 2003, 278: 29410– 29419 UR - https://dergipark.org.tr/en/pub/eujhs/issue//552057 L1 - https://dergipark.org.tr/en/download/article-file/692430 ER -