Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells

ZhouC.; PanW.; WangX.P.ChenT.S.

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Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells

机译：通过Bak-mediated青蒿琥酯诱发细胞凋亡caspase-independent内在途径在人类肺腺癌的细胞

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This report is designed to explore the exact molecular mechanism by which artesunate (ART), a semisynthetic derivative of the herbal antimalaria drug artemisinin, induces apoptosis in human lung adenocarcinoma (ASTC-a-1 and A549) cell lines. ART treatment induced ROS-mediated apoptosis in a concentration- and time-dependent fashion accompanying the loss of mitochondrial potential and subsequent release of Smac and AIF indicative of intrinsic apoptosis pathway. Blockage of casapse-8 and -9 did not show any inhibitory effect on the ART-induced apoptosis, but which was remarkably prevented by silencing AIF. Of the utmost importance, ART treatment induced the activation of Bak but not Bax, and silencing Bak but not Bax remarkably inhibited ART-induced apoptosis and AIF release. Furthermore, although ART treatment did not induced a significant down-regulation of voltage-dependent anion channel 2 (VDAC2) expression and up-regulation of Bim expression, silencing VDAC2 potently enhanced the ART-induced Bak activation and apoptosis which were significantly prevented by silencing Bim. Collectively, our data firstly demonstrate that ART induces Bak-mediated caspase-independent intrinsic apoptosis in which Bim and VDAC2 as well as AIF play important roles in both ASTC-a-1 and A549 cell lines, indicating a potential therapeutic effect of ART for lung cancer.

机译：这份报告的目的是探索的青蒿琥酯的分子机制(ART)草药的半合成衍生物抗疟疾药物青蒿素,诱发细胞凋亡在人类肺腺癌(ASTC-a-1和A549)细胞系。细胞凋亡在浓度和时间时尚伴随线粒体的损失Smac和AIF的潜在和随后的释放表明内在的细胞凋亡途径。没有任何堵塞casapse-8和9在如今细胞凋亡的抑制作用,但这是非常被沉默如果。诱导贝克的激活,但不是伯灵顿,沉默贝克但不是伯灵顿显著抑制如今细胞凋亡和AIF释放。此外,虽然没有艺术治疗诱导显著下调压敏电阻器阴离子通道2 (VDAC2)表达和老年病的Bim表达式,如今沉默VDAC2强有力地提高了贝克激活和细胞凋亡明显被压制荡妇。总的来说,我们的数据首先证明艺术诱发Bak-mediated caspase-independentBim和VDAC2固有细胞凋亡以及如果ASTC-a-1扮演重要角色和A549细胞株,表明潜力艺术对于肺癌的治疗效果。

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来源
《Journal of Cellular Physiology》 |2012年第12期|3778-3786|共9页
作者
ZhouC.; PanW.; WangX.P.ChenT.S.;
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作者单位

MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of;

Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China;

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正文语种英语
中图分类细胞生物学;
关键词
artesunate; VDAC2 gene; ApoptosisAdenocarcinoma of lung;

机译：肺;

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Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells

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