MAC related mitochondrial pathway in oroxylin A induces apoptosis in human hepatocellular carcinoma HepG2 cells
MAC related mitochondrial pathway in oroxylin A induces apoptosis in human hepatocellular carcinoma HepG2 cells
复制标题
oroxylin A中MAC相关线粒体通路诱导人肝癌HepG2细胞凋亡
DOI：
10.1016/j.canlet.2009.04.021
复制
发表时间：
2009-11-01
期刊：
影响因子：
9.7
通讯作者：
Guo, Qing-Long
中科院分区：
文献类型：
--
作者：
Liu, Wei;Mu, Rong;Guo, Qing-Long
Oroxylin A是一种从黄芩根中分离得到的黄酮类化合物。我们的前期工作表明，木脂素A的抗肿瘤活性主要是通过诱导细胞凋亡来实现的。本研究探讨了木脂素A诱导肿瘤细胞凋亡的确切分子机制。我们发现，在HepG 2细胞中，木脂素A诱导的凋亡是通过线粒体途径实现的。我们还研究了哪些线粒体通道，PTP或MAC或两者，参与了用oroxylin A处理后线粒体外膜的透化。结果表明，oroxylin A-诱导凋亡的PTP-独立的方式，因此，我们把注意力集中在MAC。由于Bax在某些系统中是MAC的重要组成部分，我们研究了经oroxylin A处理的HepG 2细胞中Bax的活化、亚细胞定位、寡聚体结构。此外，我们的研究结果表明，Bcl-2的过表达抑制了木脂素A诱导的细胞凋亡。总之，我们已经证明，开放的MAC，而不是PTP，发挥了关键作用，在乳清酸A诱导的激活线粒体凋亡途径在HepG 2细胞。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Oroxylin A is a flavonoid isolated from the root of Scutellaria baicalensis Georgi. Our previous work demonstrated that the anti-tumor activity of oroxylin A was mainly attributed to its apoptosis inducing effect in cells. The present study explores the exact molecular mechanism of oroxylin A-induced apoptosis in tumor cells. We showed that oroxylin A-induced apoptosis in HepG2 cells was achieved through mitochondrial pathway. We also investigated which mitochondrial channels, PTP or MAC or both, were involved in the permeabilization of the mitochondrial outer membrane after treatment with oroxylin A. The results showed that oroxylin A-induced apoptosis in a PTP-independent manner; therefore, we focused our attention on MAC. As Bax is an essential constituent of MAC in certain systems, we examined the activation, subcellular location, oligomeric structure of Bax in HepG2 cells treated with oroxylin A. Moreover, our results showed that overexpression of Bcl-2 inhibited oroxylin A-induced apoptosis. In summary, we have demonstrated that opening of MAC, but not PTP, played a key role in oroxylin A-induced activation of mitochondrial apoptotic pathway in HepG2 cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.