Sensitivity of Monocytic Cell Lines to Verapamil in vitro

摘要

Verapamil as a calcium channel blocker broadly used in therapy of many cardiovascular diseases such as hypertension and arrhythmia. Moreover, the anti-tumor effect of several chemotherapeutic agents has been increased by verapamil. Also, the inhibitory effect of some calcium channel blockers on tumor cell growth and invasion has been reported. Moreover, induction of apoptosis in leukemia cells by a Ca2+ channel blocker has been revealed. The present study was conducted to evaluate the verapamil cytotoxicity in two human monocytic cell lines in vitro. The human monocytic U937 and THP1 cells were cultured in complete RPMI medium. Then, the cells at logarhytmic growth phase were incubated with different concentrations of verapamil (0.01-2 mM) for 24, 48 and 72 h periods. Next, the cell viability was assessed with trypan blue dye exclusion and MTT 3-(4, 5-dimethyl thiazol-2, 5-diphenyltetrazoliumbromide) methods. Verapamil significantly decreased the proliferation of U937 and THP1 cells dose and time dependently. This cytotoxic effect after 24, 48 and 72 h incubation time was shown at ≥1, 0.2 and 0.1 mM concentration for U937 and at ≥1, 1 and 0.2 mM concentration for THP1 cells, respectively. In U937 cells verapamil cytotoxicity at 0.2 mM concentration, significantly increased with time in this order 72>48 h (p<0.05). According to the results of this study, verapamil showed a dose and time-dependent cytotoxic effect on human U937 and THP1 cells. Moreover, the sensitivity of U937 and THP1 cells to verapamil was somewhat different. So, the anti-tumor effects of verapamil reported by several investigations may be in part due to its direct cytotoxic effects. Thus, verapamil with potential inhibitory effect on leukemic U937 and THP1 cells growth might be useful as an anti-proliferative agent in leukemia.