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Dihydroartemisinin induces apoptosis in colorectal cancer cells through the mitochondria-dependent pathway

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Tumor Biology

Abstract

Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, has been shown to exhibit antitumor activity in various cancer cells, including colorectal cancer. However, the detailed mechanisms underlying its antitumor activity in colorectal cancer remain to be elucidated. In the present study, we investigated DHA-induced apoptosis in human colorectal cancer HCT-116 cells in vitro. The results showed that DHA treatment significantly reduced cell viability in a concentration- and time-dependent manner. Furthermore, DHA induced G1 cell cycle arrest, apoptotic cell death, and accumulation of reactive oxygen species (ROS). We also found that DHA decreased the mitochondrial membrane potential; activated the caspase-3, caspase-8, and caspase-9; and increased the ratio of Bax/Bcl-2. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria were observed. Strikingly, the free radical scavenger N-acetylcysteine or the caspase-3 inhibitor Ac-DEVD-CHO significantly prevented DHA-induced apoptotic cell death. Taken together, we concluded that DHA-triggered apoptosis in HCT-116 cells occurs through the ROS-mediated mitochondria-dependent pathway. Our data suggest that DHA has great potential to be developed as a novel therapeutic agent for the treatment of human colorectal cancer.

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Acknowledgement

This study was supported by a grant from the National Natural Science Foundation of China (grant no.: 81250020).

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Authors and Affiliations

  1. Department of Colorectal Surgery, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People’s Republic of China

    Min Lu, Jin Zhou & Jing Yang

  2. Seven-year System, Department of Clinical Medicine, China Medical University, Shenyang, 110001, People’s Republic of China

    Luhaoran Sun

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  1. Min Lu
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  2. Luhaoran Sun
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  3. Jin Zhou
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  4. Jing Yang
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Correspondence to Min Lu.

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Lu, M., Sun, L., Zhou, J. et al. Dihydroartemisinin induces apoptosis in colorectal cancer cells through the mitochondria-dependent pathway. Tumor Biol. 35, 5307–5314 (2014). https://doi.org/10.1007/s13277-014-1691-9

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  • DOI: https://doi.org/10.1007/s13277-014-1691-9

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