Lysosomotropic agents reverse multiple drug resistance in human cancer cells

Abstract

Chloroquine, a well-known lysosomotropic amine, partially reversed the resistance of multi-drug-resistant KB carcinoma cells to adriamycin, daunomycin, vincristine, vinblastine and actinomycin D. Other lysosomotropic amines, propranolol, atropine, amantadine and nicotine, also restored the sensitivity of multi-drug-resistant cells to the anticancer drugs. The increased rate of accumulation of [3H] daunomycin by chloroquine was more prominent in the resistant KB-ChR-24 cells than in the parental KB cells. Chloroquine inhibited the efflux of daunomycin from the resistant cells. Circumvention of multiple drug resistance in human KB carcinoma cells by the agents is discussed in relation to lysosomal function.