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

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.

• Authors: Hua Yi, Kun Wang, Biaoyan Du, Lina He, Hiuting Ho, Maosong Qiu, Yidan Zou, Qiao Li, Junfeng Jin, Yujuan Zhan, Zhongxiang Zhao, Xiaodong Liu
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 23 Issue 6 (Jun 02 2018) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 29865221 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Palmitic Acids
• aleuritolic acid

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Carcinoma, Hepatocellular (pathology)
• Hep G2 Cells
• Humans
• Liver Neoplasms (pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (metabolism)
• Palmitic Acids (pharmacology)