Guo Xiao-Xi, Guo Qiao, Li Yang, Lee Seung Ki, Wei Xue-Ning, Jin Ying-Hua
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130012, China.
Int J Mol Sci. 2012 Nov 22;13(12):15523-35. 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.
人参皂苷Rh2（G-Rh2）已被证明能诱导多种癌细胞发生凋亡性细胞死亡。然而，G-Rh2诱导细胞死亡所涉及的信号转导级联反应的细节尚不清楚。在本论文中，我们通过证明G-Rh2导致Bak和Bax迅速且显著的易位，从而阐明了G-Rh2诱导人肝癌SK-HEP-1细胞凋亡的分子机制，这随后触发了线粒体细胞色素c的释放以及随之而来的半胱天冬酶激活。有趣的是，基于小干扰RNA（siRNA）的半胱天冬酶-8基因失活有效地延迟了G-Rh2诱导的半胱天冬酶-9激活和凋亡，表明半胱天冬酶-8在G-Rh2诱导的凋亡程序中也起着重要作用。综上所述，我们的结果表明G-Rh2采用多种促凋亡途径来促使癌细胞死亡，这表明G-Rh2作为一种强大的化疗药物具有潜在作用。
