粒体自噬
自噬
细胞凋亡
活性氧
癌症研究
化学
血桂碱
细胞生物学
组织蛋白酶D
癌细胞
线粒体
生物
癌症
生物化学
立体化学
酶
遗传学
生物碱
作者
Jingjing Wang,Qi Su,Qing Wu,Kun Chen,Asmat Ullah,Mohsin Ahmad Ghauri,Yanmin Zhang
标识
DOI:10.1007/s12272-021-01356-0
摘要
Hepatocellular carcinoma (HCC) is one of the most common tumor types globally. Despite the progress made in surgical procedures and therapeutic options, HCC remains a considerable cause of cancer-related mortality. In this study, we investigated the antitumor effects of sanguinarine (Sang) on HCC and its potential mechanisms. Our findings showed that Sang impairs the acidic environment of lysosomes by inhibiting cathepsin D maturation. In addition, Sang inhibited the formation of autolysosomes in RFP-GFP-LC3 transfected cells, subsequently suppressing late mitophagy. Sang also induced reactive oxygen species (ROS)-dependent autophagy and apoptosis in HCC cells, which was significantly attenuated following treatment with a ROS scavenger. Further investigation using autophagy inhibitors revealed that sanguinarine-induced mitochondrial dysfunction and mitophagy led to mitochondrial apoptosis in HCC cells. Immunohistochemical staining of sanguinarine-treated xenograft samples revealed that it initiated and blocked autophagy. In summary, our findings suggest that in HCC cells, Sang impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis.
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