Abstract:

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

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