The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells
The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells
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DOI：
10.1016/j.febslet.2010.08.014
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发表时间：
2010-09-24
期刊：
影响因子：
3.5
通讯作者：
Chen, Min
中科院分区：
文献类型：
--
作者：
Lu, Ying-Ying;Chen, Tong-Sheng;Chen, Min
JNK抑制剂SP 600125被广泛用于抑制JNK介导的Bax活化和细胞凋亡。然而，本报告表明，SP 600125协同增强双氢青蒿素（DHA）诱导的人肺腺癌细胞凋亡，通过加速Bax易位和随后的内在凋亡途径，涉及线粒体膜去极化，细胞色素c释放，caspase-9和caspase-3激活。利用荧光恢复法对单个活细胞内GFP-Bax迁移率进行动态分析，结果表明SP 600125可加重DHA诱导的Bax迁移率下降和Bax易位。这些结果首次提出了一种新的促凋亡作用的SP 600125在DHA诱导的细胞凋亡。(c)2010年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The C-Jun N-terminal Kinase (JNK) inhibitor SP600125 is widely used to inhibit the JNK-mediated Bax activation and cell apoptosis. However, this report demonstrates that SP600125 synergistically enhances the dihydroartemisinin (DHA)-induced human lung adenocarcinoma cell apoptosis by accelerating Bax translocation and subsequent intrinsic apoptotic pathway involving mitochondrial membrane depolarization, cytochrome c release, caspase-9 and caspase-3 activation. The dynamical analysis of GFP-Bax mobility inside single living cells using fluorescence recovery after photobleaching revealed that SP600125 aggravated the DHA-induced decrease of Bax mobility and Bax translocation. These results for the first time present a novel pro-apoptotic action of SP600125 in DHA-induced apoptosis. (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.