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 output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3489-3497
Number of pages9
JournalTumor Biology
Volume36
Issue number5
DOIs
Publication statusPublished - May 2015

Fingerprint

Caspases
Leukemia
Apoptosis
Acute Myeloid Leukemia
Caspase 8
HL-60 Cells
Myeloid Cells
Anemarrhena
timosaponin AIII
Caspase 9
Saponins
p38 Mitogen-Activated Protein Kinases
Caspase 3
Western Blotting
Phosphorylation
Cell Proliferation
Cell Line
Growth
Neoplasms

Keywords

  • Acute myeloid leukemia
  • Apoptosis
  • JNK1/2 pathways
  • Timosaponin AIII

ASJC Scopus subject areas

  • Cancer Research

Cite this

Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells. / Huang, Hsin Lien; Chiang, Whei Ling; Hsiao, Pei Ching; Chien, Ming Hsien; Chen, Hui Yu; Weng, Wei Chun; Hsieh, Ming Ju; Yang, Shun Fa.

In: Tumor Biology, Vol. 36, No. 5, 05.2015, p. 3489-3497.

Research output: Contribution to journalArticle

Huang, Hsin Lien ; Chiang, Whei Ling ; Hsiao, Pei Ching ; Chien, Ming Hsien ; Chen, Hui Yu ; Weng, Wei Chun ; Hsieh, Ming Ju ; Yang, Shun Fa. / Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells. In: Tumor Biology. 2015 ; Vol. 36, No. 5. pp. 3489-3497.
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