Hispolon induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation.

Abstract

Hispolon is an active phenolic compound of Phellinus igniarius , a mushroom that has recently been shown to have antioxidant, anti-inflammatory, and anticancer activities. This study investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma Hep3B cells by using the MTT assay, DNA fragmentation, DAPI (4,6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analyses. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent and dose-dependent manner, through the induction of cell cycle arrest at S phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Hispolon-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A and E and cyclin-dependent kinase (CDK) 2, with concomitant induction of p21waf1/Cip1 and p27Kip1. Exposure of Hep3B cells to hispolon resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. Hispolon treatment also activated JNK, p38 MAPK, and ERK expression. Inhibitors of ERK (PB98095), but not those of JNK (SP600125) and p38 MAPK (SB203580), suppressed hispolon-induced S-phase arrest and apoptosis in Hep3B cells. These findings establish a mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and apoptosis in Hep3B cells.

• Authors: Guan-Jhong Huang, Jeng-Shyan Deng, Shyh-Shyun Huang, Miao-Lin Hu
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 59 Issue 13 Pg. 7104-13 (Jul 13 2011) ISSN: 1520-5118 [Electronic] United States
• PMID: 21630638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechols
• Enzyme Inhibitors
• hispolon
• Extracellular Signal-Regulated MAP Kinases

Topics

• Apoptosis (drug effects)
• Basidiomycota (chemistry)
• Carcinoma, Hepatocellular (pathology)
• Catechols (pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Humans
• Liver Neoplasms (pathology)
• Phosphorylation (drug effects)