Abstract
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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Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant 81773772 and 81903643) and the Fundamental Research Funds for the Central Universities (xjj2018167, xtr0118022 and xzy012020086).
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Wang, J., Su, Q., Wu, Q. et al. Sanguinarine impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis in human hepatocellular carcinoma cells. Arch. Pharm. Res. 44, 1025–1036 (2021). https://doi.org/10.1007/s12272-021-01356-0
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DOI: https://doi.org/10.1007/s12272-021-01356-0