POTENTIATION OF PIRARUBICIN ACTIVITY IN MULTIDRUG-RESISTANT CELLS BY RIFAMPICIN

The effect of the anti-tuberculosis drug rifampicin on pirarubicin act ivity was investigated in multidrug-resistant cells overexpressing P-g lycoprotein. Rifampicin increased the sensitivity of pirarubicin to an thracycline-resistant mouse leukemic P388 cells and significantly enha nced the cytotoxicity and intracellular accumulation of pirarubicin in resistant cells, but had no effect in parent cells, By contrast, two other rifamycins, rifamycin B and SV, had no effect on pirarubicin acc umulation in resistant cells, Rifampicin also enhanced pirarubicin-ind uced apoptosis and G(2)/M blockade on the cell cycle in resistant cell s. These results show that rifampicin enhances the cytotoxic action of pirarubicin in resistant cells, at least partly via the inhibition of cellular pirarubicin efflux.