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Ginsenoside Rh2 Induces Human Hepatoma Cell Apoptosisvia Bax/Bak Triggered Cytochrome C Release and Caspase-9/Caspase-8 Activation
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130012, China
College of Pharmacy, Seoul National University, Seoul 151-742, Korea
* Author to whom correspondence should be addressed.
Received: 4 September 2012; in revised form: 13 November 2012 / Accepted: 15 November 2012 / Published: 22 November 2012
Abstract: 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.
Keywords: apoptosis; Bax/Bak translocation; caspase activation cascade; caspase-8/Bid pathway; ginsenoside Rh2
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MDPI and ACS Style
Guo, X.-X.; Guo, Q.; Li, Y.; Lee, S.K.; Wei, X.-N.; Jin, Y.-H. Ginsenoside Rh2 Induces Human Hepatoma Cell Apoptosisvia Bax/Bak Triggered Cytochrome C Release and Caspase-9/Caspase-8 Activation. Int. J. Mol. Sci. 2012, 13, 15523-15535.
Guo X-X, Guo Q, Li Y, Lee SK, Wei X-N, Jin Y-H. Ginsenoside Rh2 Induces Human Hepatoma Cell Apoptosisvia Bax/Bak Triggered Cytochrome C Release and Caspase-9/Caspase-8 Activation. International Journal of Molecular Sciences. 2012; 13(12):15523-15535.
Guo, Xiao-Xi; Guo, Qiao; Li, Yang; Lee, Seung K.; Wei, Xue-Ning; Jin, Ying-Hua. 2012. "Ginsenoside Rh2 Induces Human Hepatoma Cell Apoptosisvia Bax/Bak Triggered Cytochrome C Release and Caspase-9/Caspase-8 Activation." Int. J. Mol. Sci. 13, no. 12: 15523-15535.