Calcium antagonists potentiate P-glycoprotein-independent anticancer drugs in chronic lymphocytic leukemia cells in vitro.

Abstract

Verapamil induced dose- and time -dependent death of CLL cells in vitro. A statistically significant effect (p = 0.0085) was noted with as little as 4 microM verapamil. The mode of cell death was apoptotic as determined by annexin positivity and condensation of verapamil-treated cells. Verapamil effectively potentiated the toxicity of cyclosporine and all the anticancer drugs mentioned above. Furthermore, nifedipine, a more specific L-type calcium channel antagonist, significantly potentiated the effect of chlorambucil against CLL cells. Interpretation and Conclusions. Calcium channel blockers enhance the effect of P-glycoprotein-independent anticancer drugs remarkably. This indicates that the death signals initiated by calcium depletion and anticancer drugs together facilitate cell death. This novel finding opens a new avenue to modulate, by using calcium channel antagonists, the effect of traditional anticancer drugs having different mechanisms of P-glycoprotein-independent action.