A novel autophagy/mitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission.

ABSTRACT: Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that liensinine, a major isoquinoline alkaloid, inhibits late-stage autophagy/mitophagy through blocking autophagosome-lysosome fusion. This effect is likely achieved via inhibiting the recruitment of RAB7A to lysosomes but not to autophagosomes. We further investigated the effects of autophagy inhibition by liensinine on the therapeutic efficacy of chemotherapeutic drugs and found that cotreatment of liensinine markedly decreased the viability and increased apoptosis in breast cancer cells treated with various chemotherapeutic agents. Mechanistically, we found that inhibition of autophagy/mitophagy

SUBMITTER: Zhou J 

PROVIDER: S-EPMC4590597 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature