Ginsenoside Rh2 induces human hepatoma cell apoptosisvia bax/bak triggered cytochrome C release and caspase-9/caspase-8 activation

• Published in: International journal of molecular sciences 2012-11, Vol.13 (12), p.15523-15535
• Main Authors: Guo, Xiao-Xi, Guo, Qiao, Li, Yang, Lee, Seung Ki, Wei, Xue-Ning, Jin, Ying-Hua
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Bax/Bak translocation; bcl-2 Homologous Antagonist-Killer Protein - metabolism; bcl-2-Associated X Protein - metabolism; Cancer; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Caspase 8 - metabolism; Caspase 9 - metabolism; caspase activation cascade; caspase-8/Bid pathway; Cell cycle; Cell death; Cell Line, Tumor; Cytochrome; Cytochromes c - metabolism; Enzyme Activation - drug effects; ginsenoside Rh2; Ginsenosides - pharmacology; Humans; Kinases; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Microscopy; Morphology; Signal transduction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms131215523

Ginsenoside Rh2 (G-Rh2) has been shown to induce apoptotic cell death in a variety of cancer cells. However, the details of the signal transduction cascade involved in G-Rh2-induced cell death is unclear. In this manuscript we elucidate the molecular mechanism of G-Rh2-induced apoptosis in human hepatoma SK-HEP-1 cells by demonstrating that G-Rh2 causes rapid and dramatic translocation of both Bak and Bax, which subsequently triggers mitochondrial cytochrome c release and consequent caspase activation. Interestingly, siRNA-based gene inactivation of caspase-8 effectively delays caspase-9 activation and apoptosis induced by G-Rh2, indicating that caspase-8 also plays an important role in the G-Rh2-induced apoptosis program. Taken together, our results indicate that G-Rh2 employs a multi pro-apoptotic pathway to execute cancer cell death, suggesting a potential role for G-Rh2 as a powerful chemotherapeutic agent.