Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells

Abstract

The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.