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Archives of Pharmacal Research

Archives of Pharmacal Research

IF: 6.9
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Sanguinarine impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis in human hepatocellular carcinoma cells.

Published:9 November 2021 DOI: PMID: 34751932
Jingjing Wang, Qi Su, Qing Wu, Kun Chen, Asmat Ullah, Mohsin Ahmad Ghauri, Yanmin Zhang

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.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
BAFILOMYCIN A1 88899-55-2 C35H58O9 303 suppliers $80.00-$2180.00
BAFILOMYCIN A1 88899-55-2 C35H58O9 303 suppliers $80.00-$2180.00
BAFILOMYCIN A1 88899-55-2 C35H58O9 303 suppliers $80.00-$2180.00
BAFILOMYCIN A1 88899-55-2 C35H58O9 303 suppliers $80.00-$2180.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone 338967-87-6 C15H10Cl2N2O2S 209 suppliers $12.00-$1200.00
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone 338967-87-6 C15H10Cl2N2O2S 209 suppliers $12.00-$1200.00

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