Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress and Mitochondrial Dysfunction Contribute to Polydatin-Induced Apoptosis in Human Nasopharyngeal Carcinoma CNE Cells
Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress and Mitochondrial Dysfunction Contribute to Polydatin-Induced Apoptosis in Human Nasopharyngeal Carcinoma CNE Cells
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DOI：
10.1002/jcb.23303
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Liao, Jianchun
中科院分区：
文献类型：
--
作者：
Liu, Huanhai;Zhao, Shuwei;Liao, Jianchun
白藜芦醇苷是一种天然小分子化合物，具有抗缺血/再灌注损伤和炎症的作用。然而，其有效的抗癌活性的作用和分子机制仍然知之甚少。在本研究中，虎杖苷以剂量和时间依赖性方式显著杀死几种人类肿瘤细胞系。该化合物还剂量依赖性地引起人鼻咽癌CNE细胞中的线粒体凋亡。此外，虎杖苷触发内质网（ER）的压力和下调Akt的磷酸化在CNE细胞，而敲低CCAAT/增强子结合蛋白同源蛋白（CHOP）显着废除Akt的失活和逆转虎杖苷的促凋亡作用。此外，虎杖苷引起CNE细胞中活性氧的产生，而抗氧化剂N-乙酰半胱氨酸几乎完全阻断了ER应激和凋亡的激活，这表明虎杖苷诱导的活性氧是触发CNE细胞中ER应激线粒体凋亡途径的早期事件。这些结果表明，虎杖苷可能是一种很有前途的抗肿瘤药物，为虎杖苷的临床应用提供了分子理论基础。J.细胞。112：3695-3703，2011. (C)2011 Wiley Periodicals，Inc.
Previous studies revealed that polydatin, a natural small compound, possessed protective effect against ischemia/reperfusion injury and inflammation. However, the action and molecular mechanism of its potent anti-cancer activity remain poorly understood. In the present study, polydatin significantly killed several human tumor cell lines in a dose- and time-dependent manner. The compound also dose-dependently caused mitochondrial apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, polydatin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt in CNE cells, while knock-down of CCAAT/enhancer-binding protein homologous protein (CHOP) dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of polydatin. Furthermore, polydatin provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting polydatin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in CNE cells. Taken together, these findings strongly suggest that polydatin might be a promising anti-tumor drug and our data provide the molecular theoretical basis for clinical application of polydatin. J. Cell. Biochem. 112: 3695-3703, 2011. (C) 2011 Wiley Periodicals, Inc.