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Molecules 2018, 23(6), 1338; https://doi.org/10.3390/molecules23061338

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

1
Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
2
Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
3
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong 999077, China
4
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
5
Department of Pathology, Zunyi Medical College (Zhuhai Campus), 519000 Zhuhai, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 24 March 2018 / Revised: 28 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products)
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Abstract

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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