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Sanguinarine impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis in human hepatocellular carcinoma cells.
Wang, Jingjing; Su, Qi; Wu, Qing; Chen, Kun; Ullah, Asmat; Ghauri, Mohsin Ahmad; Zhang, Yanmin.
Afiliación
  • Wang J; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Su Q; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Wu Q; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Chen K; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Ullah A; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Ghauri MA; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.
  • Zhang Y; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China. zhang2008@mail.xjtu.edu.cn.
Arch Pharm Res ; 44(11): 1025-1036, 2021 Nov.
Article en En | MEDLINE | ID: mdl-34751932
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Benzofenantridinas / Isoquinolinas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arch Pharm Res Año: 2021 Tipo del documento: Article Pais de publicación: Corea del Sur
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Benzofenantridinas / Isoquinolinas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arch Pharm Res Año: 2021 Tipo del documento: Article Pais de publicación: Corea del Sur