Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells.

Abstract

The anti-cancer activities of Thonningianin A on the HepG-2 human hepatocellular carcinoma cell line were evaluated by MTT assay, flow cytometry, quantitative real-time PCR and western blotting. Results showed that Thonningianin A effectively inhibited the proliferation of HepG-2 cells by inducing apoptosis, as evidenced by increase in the sub-G1 cell population, DNA fragmentation, and increase in the content of reactive oxygen species. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that Thonningianin A-induced apoptosis is caspase-dependent. Thonningianin A also disrupted the mitochondrial membrane potential (Δψm) and down-regulated the Bcl-xL mRNA expression in HepG-2 cells. Thonningianin A induced cell cycle arrest by changing the cyclin D1 and CDK4 mRNA expression levels. Moreover, western blotting showed that Thonningianin A significantly down-regulated the NF-kappa-B cell survival pathway, along with up-regulation of the expression level of phosphorylated P38 and down-regulation of the expression level of phosphorylated ERK. The anti-cancer activity of Thonningianin A was confirmed by the characteristic patterns of DNA fragmentation and cell cycle arrest, suggesting that Th A is an effective antitumor ingredient in natural plant foods, and is worthy of further study.

• Authors: Tian-Tian Zhang, Li Yang, Jian-Guo Jiang
• Journal: Food & function (Food Funct) Vol. 6 Issue 8 Pg. 2588-97 (Aug 2015) ISSN: 2042-650X [Electronic] England
• PMID: 26119846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrolyzable Tannins
• thonningianin A
• Cyclin D1
• Caspase 3
• Caspase 9

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, enzymology, genetics, physiopathology)
• Caspase 3 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D1 (genetics, metabolism)
• Hep G2 Cells
• Humans
• Hydrolyzable Tannins (pharmacology)
• Liver Neoplasms (drug therapy, enzymology, genetics, physiopathology)