The reversal of doxorubicin resistance by verapamil is not due to an effect on calcium channels

Abstract

Using a model of doxorubicin-resistant rat glioblastoma cells, we have studied the relationship between the reversal of multi-drug resistance by verapamil and calcium fluxes into the cells. Although it is known to be a voltage-dependent calcium channel blocker, verapamil exerted no effect on calcium entry into the cells. In the absence of calcium in the medium, drug resistance was not affected and verapamil was still active. It was possible to modify calcium fluxes into the cells by using manganese ions (decreasing calcium uptake) or the calcium ionophore A23187 (increasing calcium uptake). These agents had only a marginal effect on the expression of drug resistance by the cells and did not prevent the action of verapamil on its reversal.