Verapamil reverses the ultrastructural alterations in the plasma membrane induced by drug resistance

Two P388 cell sublines with different levels of resistance to daunomycin (DNM), P388/20 and P388/100 cells (∼ 20- and 100-fold resistance, respectively), undergo a significant (∼ 2-fold) increase in the number of intramembrane particles (IMPS) present at their plasma membrane, as compared to that exhibited by the parental, drug-sensitive P388 (P388/S) cell line. Regardless of the level of resistance, incubation of drug-resistant cells with verapamil, a well known reverting agent of anthracycline resistance, restores the morphology of the plasma membrane in these cells, yielding a pattern in which the number and size distribution of IMPs at both leaflets of the bilayer, become undistinguishable from those displayed by drug-sensitive celIs. Furthermore, verapamil did not affect the ultrastructural organization of the plasma membrane of drug-sensitive cells. It is possible that the alterations in the structural organization of the plasma membrane of the antineoplastic-resistant tumor cells, might represent a reliable 'marker' for early diagnosis of drug resistance.