부산대학교 도서관

Hepatocellular carcinoma (HCC) is one of themost common tumor types globally. Despite the progressmade in surgical procedures and therapeutic options, HCCremains a considerable cause of cancer-related mortality. In this study, we investigated the antitumor eff ects of sanguinarine(Sang) on HCC and its potential mechanisms. Our fi ndings showed that Sang impairs the acidic environmentof lysosomes by inhibiting cathepsin D maturation. Inaddition, Sang inhibited the formation of autolysosomes inRFP-GFP-LC3 transfected cells, subsequently suppressinglate mitophagy. Sang also induced reactive oxygen species(ROS)-dependent autophagy and apoptosis in HCC cells,which was signifi cantly attenuated following treatment witha ROS scavenger. Further investigation using autophagyinhibitors revealed that sanguinarine-induced mitochondrialdysfunction and mitophagy led to mitochondrial apoptosisin HCC cells. Immunohistochemical staining of sanguinarine-treated xenograft samples revealed that it initiated andblocked autophagy. In summary, our fi ndings suggest thatin HCC cells, Sang impairs lysosomal function and inducesROS-dependent mitophagy and apoptosis.