Resveratrol Induces Apoptosis of Human Nasopharyngeal Carcinoma Cells Via Activation of Multiple Apoptotic Pathways
Resveratrol Induces Apoptosis of Human Nasopharyngeal Carcinoma Cells Via Activation of Multiple Apoptotic Pathways
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DOI：
10.1002/jcp.22391
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发表时间：
2011-03-01
影响因子：
5.6
通讯作者：
Lai, Hsin-Chih
中科院分区：
文献类型：
--
作者：
Huang, Tsung-Teng;Lin, Hung-Chi;Lai, Hsin-Chih
白藜芦醇是一种天然存在的饮食化合物，具有化学预防特性，据报道可引发多种类型的癌细胞凋亡。白藜芦醇是否对人鼻咽癌(NPC)细胞有任何活性仍有待确定。本研究旨在探讨白藜芦醇对人鼻咽癌细胞的作用及其机制。白藜芦醇处理后，鼻咽癌细胞存活率显著下降，且呈剂量和时间依赖性。流式细胞术分析显示细胞凋亡量呈剂量依赖关系。细胞凋亡的分子机制研究表明，白藜芦醇处理可导致线粒体跨膜电位显著降低，细胞色素c释放，Fas配体(FasL)表达增强，葡萄糖调节蛋白78 kDa(GRP78)表达受抑。紧随其后的是caspase-9、-8、-4和-3的激活，随后导致DNA断裂和细胞凋亡。此外，还观察到促凋亡的Bax表达上调，抗凋亡的Bcl2蛋白表达下调。综上所述，白藜芦醇通过调节死亡受体、线粒体和内质网应激等多种凋亡途径诱导人鼻咽癌细胞凋亡。白藜芦醇可作为治疗鼻咽癌的有效化合物。J.细胞。物理。226：720-728,2011。(C)2010年Wiley-Liss公司
Resveratrol, a naturally occurring dietary compound with chemopreventive properties has been reported to trigger a variety of cancer cell types to apoptosis. Whether resveratrol shows any activity on human nasopharyngeal carcinoma (NPC) cells remained to be determined. The aim of this study was to investigate the effect and mechanism of resveratrol on human NPC cells. Treatment of resveratrol resulted in significant decrease in cell viability of NPC cell lines in a dose- and time-dependent manner. A dose- dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled resveratrol treatment resulted in a significant loss of mitochondrial transmembrane potential, release of cytochrome c, enhanced expression of Fas ligand (FasL), and suppression of glucose-regulated protein 78 kDa (GRP78). These were followed by activation of caspases-9, -8, -4, and -3, subsequently leading to DNA fragmentation and cell apoptosis. Furthermore, up-regulation of proapoptotic Bax and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, resveratrol induces apoptosis in human NPC cells through regulation of multiple apoptotic pathways, including death receptor, mitochondria, and endoplasmic reticulum (ER) stress. Resveratrol can be developed as an effective compound for human NPC treatment. J. Cell. Physiol. 226: 720-728, 2011. (C) 2010 Wiley-Liss, Inc.