Tumor Biology

, Volume 36, Issue 5, pp 3489–3497 | Cite as

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

  • Hsin-Lien Huang
  • Whei-Ling Chiang
  • Pei-Ching Hsiao
  • Ming-Hsien Chien
  • Hui-Yu Chen
  • Wei-Chun Weng
  • Ming-Ju Hsieh
  • Shun-Fa Yang
Research Article

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.

Keywords

Timosaponin AIII Apoptosis JNK1/2 pathways Acute myeloid leukemia 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hsin-Lien Huang
    • 1
  • Whei-Ling Chiang
    • 2
    • 3
  • Pei-Ching Hsiao
    • 4
    • 5
  • Ming-Hsien Chien
    • 6
    • 7
  • Hui-Yu Chen
    • 1
  • Wei-Chun Weng
    • 1
    • 8
  • Ming-Ju Hsieh
    • 1
    • 9
    • 10
  • Shun-Fa Yang
    • 1
    • 3
  1. 1.Institute of MedicineChung Shan Medical UniversityTaichungTaiwan
  2. 2.School of Medical Laboratory and BiotechnologyChung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of Medical ResearchChung Shan Medical University HospitalTaichungTaiwan
  4. 4.School of MedicineChung Shan Medical UniversityTaichungTaiwan
  5. 5.Department of Internal MedicineChung Shan Medical University HospitalTaichungTaiwan
  6. 6.Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  7. 7.Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  8. 8.Division of Urology, Department of SurgeryTungs’ Taichung MetroHarbor HospitalTaichungTaiwan
  9. 9.Cancer Research CenterChanghua Christian HospitalChanghuaTaiwan
  10. 10.School of OptometryChung Shan Medical UniversityTaichungTaiwan

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