Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress
Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress
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DOI：
10.1177/0960327111417269
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发表时间：
2012-06-01
影响因子：
2.8
通讯作者：
Chung, J-G
中科院分区：
文献类型：
--
作者：
Ip, S-W;Lan, S-H;Chung, J-G
辣椒素是一种存在于辣椒中的刺激性化合物，对多种肿瘤细胞具有抗肿瘤活性，但其诱导鼻咽癌细胞凋亡的机制尚不清楚。在这里，我们研究了辣椒素诱导人NPC（NPC-TW 039）细胞凋亡的分子机制。辣椒素的影响涉及内质网（ER）应激，caspase-3激活和线粒体去极化。辣椒素通过G 0/G1期阻滞和以剂量依赖性方式诱导NPC-TW 039细胞凋亡诱导细胞毒性效应（细胞死亡）。辣椒素处理通过促进活性氧（ROS）的产生、增加肌醇需要酶I（IRE I）、生长停滞和DNA损伤诱导蛋白153（GADD 153）和葡萄糖调节蛋白78（GRP 78）的水平来触发ER应激。其他效应包括胞质Ca 2+增加、线粒体跨膜电位（Delta Psi（m））丧失、细胞色素c和凋亡诱导因子（AIF）释放以及半胱天冬酶-9和-3活化。此外，辣椒素诱导的Bax/Bcl-2的比例和丰富的凋亡相关蛋白水平的增加。这些结果表明，内质网应激和细胞凋亡介导的细胞死亡参与辣椒素诱导的NPC-TW 039细胞凋亡。
Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring I enzyme (IRE I), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca2+, loss of the mitochondrial transmembrane potential (Delta Psi(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.