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Artemisinin induces A549 cell apoptosis dominantly via a reactive oxygen species-mediated amplification activation loop among caspase-9, -8 and -3

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Abstract

This report is designed to explore the roles of caspase-8, -9 and -3 in artemisinin (ARTE)-induced apoptosis in non-small cell lung cancer cells (A549 cells). ARTE induced reactive oxygen species (ROS)-mediated apoptosis in dose- and time-dependent fashion. Although ARTE treatment did not induce Bid cleavage and significant loss of mitochondrial membrane potential, it induced release of Smac and AIF but not cytochrome c from mitochondria, and silencing of Bak but not Bax significantly prevented ARTE-induced cytotoxicity. Moreover, ARTE treatment induced ROS-dependent activation of caspase-9, -8 and -3. Of the utmost importance, silencing or inhibiting any one of caspase-8, -9 and -3 almost completely prevented ARTE-induced activation of all the three caspases and remarkably abrogated the cytotoxicity of ARTE, suggesting that ARTE triggered an amplification activation loop among caspase-9, -8 and -3. Collectively, our data demonstrate that ARTE induces a ROS-mediated amplification activation loop among caspase-9, -8 and -3 to dominantly mediate the apoptosis of A549 cells.

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Acknowledgments

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, College of Biophotonics, South China Normal University, Guangzhou, 510631, China

    Weijie Gao, Fenglian Xiao & Tongsheng Chen

  2. College of Life Science, South China Normal University, Guangzhou, 510631, China

    Fenglian Xiao

  3. Department of Pain Management, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China

    Xiaoping Wang

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  1. Weijie Gao
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  2. Fenglian Xiao
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  3. Xiaoping Wang
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  4. Tongsheng Chen
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Correspondence to Tongsheng Chen.

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W. Gao and F. Xiao contributed equally to this work.

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Gao, W., Xiao, F., Wang, X. et al. Artemisinin induces A549 cell apoptosis dominantly via a reactive oxygen species-mediated amplification activation loop among caspase-9, -8 and -3. Apoptosis 18, 1201–1213 (2013). https://doi.org/10.1007/s10495-013-0857-z

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  • DOI: https://doi.org/10.1007/s10495-013-0857-z

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