Co-Treatment With Ginsenoside Rh2 and Betulinic Acid Synergistically Induces Apoptosis in Human Cancer Cells in Association With Enhanced Capsase-8 Activation, Bax Trans location, and Cytochrome c Release
Co-Treatment With Ginsenoside Rh2 and Betulinic Acid Synergistically Induces Apoptosis in Human Cancer Cells in Association With Enhanced Capsase-8 Activation, Bax Trans location, and Cytochrome c Release
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DOI：
10.1002/mc.20673
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发表时间：
2011-10-01
影响因子：
4.6
通讯作者：
Jin, Ying-Hua
中科院分区：
文献类型：
--
作者：
Li, Qing;Li, Yang;Jin, Ying-Hua
我们首次提供了两种天然化合物G-Rh 2（G-Rh 2）和桦木酸（BetA）协同诱导人宫颈腺癌（HeLa）、人肺癌A549和人肝癌HepG 2细胞凋亡的证据。G-Rh 2和Bet A协同诱导Bax向线粒体的移位和细胞色素c的释放。G-Rh 2和Bet A的共处理导致caspase-8和Bid的切割增强。siRNA技术特异性抑制caspase-8可有效抑制caspase-9的加工、聚腺苷二磷酸核糖聚合酶（PARP）的裂解、caspase-3的激活和凋亡，提示caspase-8反馈放大途径可能参与了凋亡过程。先前的研究表明，G-Rh 2通过Bcl-2和/或Bcl-xL非依赖性机制诱导癌细胞凋亡，而Bet A主要通过具有肿瘤特异性的线粒体途径诱导凋亡。由于抗凋亡的Bcl-2和Bcl-xL在人癌细胞中经常过表达，因此G-Rh 2和Bet A的联合治疗可能是增强抗癌治疗功效的新策略。(C)2011 Wiley-Liss，Inc.
We provide evidence for the first time, that two natural compounds ginsenoside Rh2 (G-Rh2) and betulinic acid (Bet A) synergistically induce apoptosis in human cervical adenocarcinoma (HeLa), human lung cancer A549, and human hepatoma HepG2 cells. G-Rh2 and Bet A cooperated to induce Bax traslocation to mitochondria and cytochrome c release. Co-treatment of G-Rh2 and Bet A resulted in enhanced cleavage of caspase-8 and Bid. Moreover, specific inhibition of caspase-8 by siRNA technology effectively reduced caspase-9 processing, poly (ADP-ribose) polymerase (PARP) cleavage, caspase-3 activation, and apoptosis in co-treated cells, which indicated that the caspase-8 feedback amplification pathway may have been involved in the apoptosis process. A previous study has shown that G-Rh2 induces cancer cell apoptosis via a Bcl-2 and/or Bcl-xL-independent mechanism, and Bet A induces apoptosis mainly through a mitochondrial pathway with tumor specificity. Since the antiapoptotic BcI-2 and Bcl-xL are frequently overexpressed in human cancer cells, combined treatment with G-Rh2 and Bet A may be a novel strategy to enhance efficacy of anticancer therapy. (C) 2011 Wiley-Liss, Inc.