Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic cancer cells.
Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic cancer cells.
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DOI：
10.1155/2013/629750
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Tong H
中科院分区：
文献类型：
--
作者：
Lin S;Zhang J;Chen H;Chen K;Lai F;Luo J;Wang Z;Bu H;Zhang R;Li H;Tong H
辣椒素是辣椒中的主要辛辣成分，它通过多种机制对多种癌细胞具有抗癌作用。在这项研究中，我们研究了辣椒素对人胰腺癌细胞在体外和体内系统的凋亡作用，以及可能的机制。在体外实验中，辣椒素处理胰腺癌细胞（PANC-1和SW 1990）导致细胞生长抑制，G 0/G1期阻滞，并以剂量依赖的方式凋亡。生长停滞和DNA损伤诱导基因153（GADD 153），内质网应激（ERS-）介导的细胞凋亡途径的标志物，通过特异性siRNA的敲低减弱辣椒素诱导的PANC-1和SW 1990细胞凋亡。此外，体内研究表明辣椒素能有效抑制胰腺癌的生长和代谢，延长胰腺癌异种移植瘤诱导小鼠的生存时间。此外，辣椒素增加了一些关键的ERS标志物的表达，包括葡萄糖调节蛋白78（GRP 78），磷蛋白激酶样内质网激酶（phosphoPERK），磷酸化真核起始因子-2 α（phospho-eIF 2 α），转录激活因子4（ATF 4）和GADD 153在肿瘤组织中。综上所述，我们首次提供了重要的证据支持ERS参与辣椒素诱导胰腺癌细胞凋亡。
Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990) with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153), a marker of the endoplasmic-reticulum-stress- (ERS-) mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78), phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK), and phosphoeukaryotic initiation factor-2α (phospho-eIF2α), activating transcription factor 4 (ATF4) and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.
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