Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress
Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress
复制标题
漆树酸诱导与 ATF4 依赖性内质网应激相关的细胞凋亡。
DOI：
10.1016/j.toxlet.2014.05.012
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发表时间：
2014-08-04
影响因子：
3.5
通讯作者：
Liu, Jinbao
中科院分区：
文献类型：
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作者：
Huang, Hongbiao;Hua, Xianliang;Liu, Jinbao
十五烷基水杨酸(6-十五烷基水杨酸，AA)是从传统药材长春花中分离得到的一种天然化合物，具有抗肿瘤活性。然而，它的分子靶点还没有得到彻底的研究。在这里，我们报告AA是内质网(ER)应激的有效诱导者，导致肝癌HepG2和骨髓瘤U266细胞的凋亡。在HepG2和U266细胞中，AA诱导的ER信号下游分子如GRP78/Bip、磷酸化eIF2α、ATF4和CHOP的表达呈剂量和时间依赖性增加。SiRNA阻断ATF4的表达部分地抑制了这些细胞，而siRNA抑制CHOP的表达则略微增加了AA诱导的细胞死亡。此外，AA抑制了HepG2异种移植瘤的生长，与体内ER应激增加有关。这些结果提示，AA诱导肿瘤细胞凋亡与ATF4依赖的内质网应激有关。(C)2014年，爱思唯尔爱尔兰有限公司出版。
Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygium adstringens, has been reported to possess antitumor activities. However, its molecular targets have not been thoroughly studied. Here, we report that AA is a potent inducer of endoplasmic reticulum (ER) stress, leading to apoptosis in hepatoma HepG2 and myeloma U266 cells. Induction of ER stress by AA was supported by a dose- and time-dependent increase in expression of the ER signaling downstream molecules, such as GRP78/BiP, phosphorylated eIF2 alpha, ATF4 and CHOP in both HepG2 and U266 cell lines. Blockage of ATF4 expression by siRNA partially inhibited, while knockdown of CHOP expression by siRNA slightly increased AA-induced cell death in these cells. In addition, AA suppressed HepG2 xenograft tumor growth, associated with increased ER stress in vivo. These results suggest that AA induces tumor cell apoptosis associated with ATF4-dependent ER stress. (C) 2014 Published by Elsevier Ireland Ltd.