Amplification activation loop between caspase-8 and -9 dominates artemisinin-induced apoptosis of ASTC-a-1 cells
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- 作者：Fenglian Xiao (1)
Weijie Gao (1)
Xiaoping Wang (2)
Tongsheng Chen (1) chentsh@scnu.edu.cn - 关键词：Artemisinin (ARTE) – ; Apoptosis – ; Caspases – ; Amplification activation loop – ; ASTC ; a ; 1 cells
- 刊名：Apoptosis
- 出版年：2012
- 出版时间：June 2012
- 年：2012
- 卷：17
- 期：6
- 页码：600-611
- 全文大小：483.8 KB
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- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Cancer Research
Cell Biology
Biochemistry
Virology - 出版者：Springer Netherlands
- ISSN：1573-675X
文摘
Although caspases have been demonstrated to be involved in artemisinin (ARTE)-induced apoptosis, their exact functions are not well understood. The aim of this report is to explore the roles of caspase-8, -9 and -3 during ARTE-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. ARTE treatment induces a rapid generation of reactive oxygen species (ROS), and ROS-dependent apoptosis as well as the activation of caspase-8, -9 and -3 via time- and dose-dependent fashion. Of upmost importance, inhibition of caspase-8 or -9, but not caspase-3, almost completely blocks the ARTE-induced not only activation of the caspase-8, -9 and -3 but also apoptosis. In addition, the apoptotic process triggered by ARTE does not involve the Bid cleavage, tBid translocation, significant loss of mitochondrial membrane potential and cytochrome c release from mitochondria. Moreover, silencing Bax/Bak does not prevent the ATRE-induced cell death as well as the activation of caspase-8, -9 and -3. Collectively, our data firstly demonstrate that ARTE triggers a ROS-mediated positive feedback amplification activation loop between caspase-8 and -9 independent of mitochondria, which dominantly mediated the ARTE-induced apoptosis via a caspase-3-independent apoptotic pathway in ASTC-a-1 cells. Our findings imply a potential to develop new derivatives from artemisinin to effectively initiate the amplification activation loop of caspases.