Involvement of up-regulation of PUMA in non-steroidal anti-inflammatory drug-induced apoptosis
Involvement of up-regulation of PUMA in non-steroidal anti-inflammatory drug-induced apoptosis
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DOI：
10.1016/j.bbrc.2007.03.034
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发表时间：
2007-05-11
影响因子：
3.1
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
--
作者：
Ishihara, Tomoaki;Hoshino, Tatsuya;Mizushima, Tohru
NSAID如塞来昔布诱导癌细胞凋亡。虽然这种凋亡效应与此类药物的抗肿瘤活性有关，但其发生机制尚未完全了解。我们在这里报告，各种非甾体类抗炎药，包括塞来昔布，上调的Bcl-2家族蛋白，具有强大的凋亡诱导活性，在人胃癌细胞系，伴随着诱导凋亡。使用siRNA和细胞内Ca 2+螯合剂的实验显示，ATF 4和CHOP的Ca 2+依赖性上调参与了ATF 4和CHOP A的这种上调。siRNA抑制塞来昔布诱导的Bax的激活和易位，细胞色素c释放到胞质溶胶和诱导细胞凋亡，这表明ESTAIA在塞来昔布诱导的线粒体功能障碍和导致的细胞凋亡中起重要作用。(c)2007爱思唯尔公司All rights reserved.
NSAIDs such as celecoxib induce apoptosis in cancer cells. Although this apoptotic effect is involved in the anti-tumor activity associated with such drugs, the mechanism by which this occurs is not fully understood. We report here that various NSAIDs, including celecoxib, up-regulate PUMA, a Bcl-2 family protein with potent apoptosis-inducing activity, in human gastric carcinoma cell line, accompanying the induction of apoptosis. Experiments using siRNA and an intracellular Ca2+ chelator revealed that Ca2+-dependent up-regulation of ATF4 and CHOP is involved in this up-regulation of PUMA. The siRNA for PUMA inhibited the celecoxib-induced activation and translocation of Bax, release of cytochrome c into the cytosol and induction of apoptosis, suggesting that PUMA plays an important role in celecoxib-induced mitochondrial dysfunction and the resulting apoptosis. (c) 2007 Elsevier Inc. All rights reserved.