期刊
ARCHIVES OF PHARMACAL RESEARCH
卷 44, 期 11, 页码 1025-1036出版社
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-021-01356-0
关键词
Sanguinarine; Lysosomal function; Reactive oxygen species; Mitophagy; Apoptosis; Hepatocellular carcinoma
资金
- National Natural Science Foundation of China [81773772, 81903643]
- Fundamental Research Funds for the Central Universities [xjj2018167, xtr0118022, xzy012020086]
This study investigated the antitumor effects of sanguinarine (Sang) on hepatocellular carcinoma (HCC) and found that Sang impairs lysosomal function, induces ROS-dependent mitophagy and apoptosis in HCC cells. The findings suggest that Sang could be a potential therapeutic option for treating HCC by targeting these mechanisms.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据