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Amplification activation loop between caspase-8 and -9 dominates artemisinin-induced apoptosis of ASTC-a-1 cells

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Abstract

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.

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Acknowledgment

We thank Dr. K. Taira for providing CFP-Bid plasmid and Dr. Y. Gotoh for providing DsRed-Mito plasmid. This work was supported by National Natural Science Foundation of China (31071218, 61178078 and 81071491) and Key Project of the Department of Education and Finance of Guangdong Province (cxzd115).

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Authors and Affiliations

  1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China

    Fenglian Xiao, Weijie Gao & Tongsheng Chen

  2. Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China

    Xiaoping Wang

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  1. Fenglian Xiao
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  3. Xiaoping Wang
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Correspondence to Tongsheng Chen.

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Fenglian Xiao and Weijie Gao contribute equally to this paper.

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Xiao, F., Gao, W., Wang, X. et al. Amplification activation loop between caspase-8 and -9 dominates artemisinin-induced apoptosis of ASTC-a-1 cells. Apoptosis 17, 600–611 (2012). https://doi.org/10.1007/s10495-012-0706-5

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