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Aleuritolic Acid Impaired Autophagic Flux and Induced Apoptosis in Hepatocellular Carcinoma HepG2 Cells

Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong 999077, China
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
Department of Pathology, Zunyi Medical College (Zhuhai Campus), 519000 Zhuhai, China
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2018, 23(6), 1338;
Received: 24 March 2018 / Revised: 28 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
PDF [23061 KB, uploaded 2 June 2018]


Aleuritolic acid (AA) is a triterpene that is isolated from the root of Croton crassifolius Geisel. In the present study, the cytotoxic effects of AA on hepatocellular carcinoma cells were evaluated. AA exerted dose- and time-dependent cytotoxicity by inducing mitochondria-dependent apoptosis in the hepatocellular carcinoma cell line, HepG2. Meanwhile, treatment with AA also caused dysregulation of autophagy, as evidenced by enhanced conversion of LC3-I to LC3-II, p62 accumulation, and co-localization of GFP and mCherry-tagged LC3 puncta. Notably, blockage of autophagosome formation by ATG5 knockdown or inhibitors of phosphatidylinositol 3-kinase (3-MA or Ly294002), significantly reversed AA-mediated cytotoxicity. These data indicated that AA retarded the clearance of autophagic cargos, resulting in the production of cytotoxic factors and led to apoptosis in hepatocellular carcinoma cells. View Full-Text
Keywords: aleuritolic acid; autophagy; apoptosis aleuritolic acid; autophagy; apoptosis

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Yi, H.; Wang, K.; Du, B.; He, L.; HO, H.; Qiu, M.; Zou, Y.; Li, Q.; Jin, J.; Zhan, Y.; Zhao, Z.; Liu, X. Aleuritolic Acid Impaired Autophagic Flux and Induced Apoptosis in Hepatocellular Carcinoma HepG2 Cells. Molecules 2018, 23, 1338.

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