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Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells

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Tumor Biology

Abstract

Timosaponin AIII (TAIII) is a steroidal saponin isolated from Anemarrhena asphodeloides that has been shown to inhibit cell growth and induce apoptosis in cancer. However, the effect of TAIII on acute myeloid leukemia (AML) remains unclear. Here, the molecular mechanism by which TAIII-induced apoptosis affects human AML cells was investigated. The results showed that TAIII significantly inhibited cell proliferation of four AML cell lines (MV4-11, U937, THP-1, and HL-60). Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. Taken together, our results suggest that TAIII induces HL-60 cell apoptosis through JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML.

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Authors and Affiliations

  1. Institute of Medicine, Chung Shan Medical University, 110, Section 1, Chien-Kuo N. Road, Taichung, 40201, Taiwan

    Hsin-Lien Huang, Hui-Yu Chen, Wei-Chun Weng, Ming-Ju Hsieh & Shun-Fa Yang

  2. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Whei-Ling Chiang

  3. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

    Whei-Ling Chiang & Shun-Fa Yang

  4. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Pei-Ching Hsiao

  5. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    Pei-Ching Hsiao

  6. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ming-Hsien Chien

  7. Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Ming-Hsien Chien

  8. Division of Urology, Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan

    Wei-Chun Weng

  9. Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan

    Ming-Ju Hsieh

  10. School of Optometry, Chung Shan Medical University, Taichung, Taiwan

    Ming-Ju Hsieh

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  1. Hsin-Lien Huang
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Correspondence to Ming-Ju Hsieh or Shun-Fa Yang.

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Hsin-Lien Huang and Whei-Ling Chiang contributed equally to this work.

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Huang, HL., Chiang, WL., Hsiao, PC. et al. Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells. Tumor Biol. 36, 3489–3497 (2015). https://doi.org/10.1007/s13277-014-2985-7

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  • DOI: https://doi.org/10.1007/s13277-014-2985-7

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