Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells
Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells
复制标题
内质网应激导致维生素E琥珀酸盐诱导人胃癌SGC-7901细胞凋亡
DOI：
10.1016/j.canlet.2010.04.002
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发表时间：
2010-10-01
期刊：
影响因子：
9.7
通讯作者：
Wu, Kun
中科院分区：
文献类型：
--
作者：
Huang, Xiaoli;Zhang, Zhihong;Wu, Kun
维生素E琥珀酸酯（rrr - α -生育酚琥珀酸酯，VES）是一种有效的细胞凋亡诱导剂，是治疗癌症的有效药物。然而，VES介导这种效应的机制尚不完全清楚。本实验研究了内质网应激和未折叠蛋白反应（UPR）对vess诱导的人胃癌细胞SGC-7901凋亡的影响。VES引起典型的细胞凋亡、内质网扩张和胞浆Ca2+浓度增加的细胞学改变。内源性内质网应激标志物GRP78和GRP94在转录和翻译上发生改变。对VES的反应，观察到CHOP的诱导、caspase-4和JNK的激活。此外，VES还以浓度和时间依赖的方式触发UPR组分的激活，包括rna依赖性蛋白激酶（PKR）样ER激酶（PERK）、激活转录因子6 （ATF6）、x- box结合蛋白1 （XBP1）和ATF4。因此，我们的研究结果表明，在SGC-7901人胃癌细胞中，vess诱导的凋亡与内质网应激和UPR激活有关。2010爱思唯尔爱尔兰有限公司版权所有。
Vitamin E succinate (RRR-alpha-tocopheryl succinate, VES), an efficient inducer of apoptosis acts as a potent agent for cancer therapy. However, the mechanism by which VES mediates the effects are not yet fully understood. Here we studied the effect of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) on VES-induced apoptosis of SGC-7901 human gastric cancer cells. VES caused cytological changes typical of apoptosis, increased ER dilation and cytosolic Ca2+ concentration. And endogenous ER stress markers, GRP78 and GRP94 were transcriptionally and translationally altered. In response to VES, induction of CHOP, activation of caspase-4 and JNK were observed. Furthermore, VES also triggered activation of UPR components, including RNA-dependent protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), X-box-binding protein 1 (XBP1), and ATF4 in a concentration- and time-dependent manner. Consequently, our results suggest that VES-induced apoptosis is coupled to ER stress and UPR activation in SGC-7901 human gastric cancer cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.