College of Natural Resources and Life Science, BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Republic of Korea.
J Agric Food Chem. 2012 May 30;60(21):5400-6. doi: 10.1021/jf3014475. Epub 2012 May 15.
Apoptosis, the main type of programmed cell death, plays an essential role in a variety of biological events. Whereas "classical" apoptosis is dependent on caspase activation, caspase-independent death is increasingly recognized as an alternative pathway. To develop new anticancer agents, oleifolioside A was isolated from Dendropanax morbifera Leveille and the biochemical mechanisms of oleifolioside A-induced apoptosis in HeLa cells were investigated. Exposure to oleifolioside A resulted in caspase activation and typical features of apoptosis, although cell death was not prevented by caspase inhibition. Oleifolioside A treatment induced up-regulation of Bad, loss of mitochondrial membrane potential, nuclear relocation of mitochondrial factors, apoptosis-inducing factor (AIF), endonuclease G (EndoG), and apoptosis induction. This is the first report of anticancer activity of oleifolioside A, and nuclear translocation of AIF and EndoG in oleifolioside A-treated HeLa cells might represent an alternative death signaling pathway in the absence of caspase activity.
细胞凋亡是一种程序性细胞死亡的主要类型，在各种生物事件中发挥着重要作用。虽然“经典”的细胞凋亡依赖于半胱氨酸天冬氨酸蛋白酶（caspase）的激活，但 caspase 非依赖性死亡正逐渐被认为是一种替代途径。为了开发新的抗癌药物，从密花八角中分离出冬绿油醇 A，并研究了冬绿油醇 A 诱导 HeLa 细胞凋亡的生化机制。尽管 caspase 抑制不能阻止细胞死亡，但暴露于冬绿油醇 A 会导致半胱氨酸天冬氨酸蛋白酶的激活和典型的凋亡特征。冬绿油醇 A 处理诱导 Bad 的上调、线粒体膜电位的丧失、线粒体因子、凋亡诱导因子（AIF）、内切核酸酶 G（EndoG）和凋亡诱导的核重定位。这是冬绿油醇 A 抗癌活性的首次报道，并且 AIF 和 EndoG 在冬绿油醇 A 处理的 HeLa 细胞中的核易位可能代表了 caspase 活性缺失时的另一种死亡信号通路。
