Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 7, pp 881–893

Antitumor effect of β-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death

  • G. Wang
  • X. Li
  • F. Huang
  • J. Zhao
  • H. Ding
  • C. Cunningham
  • J. E. Coad
  • D. C. Flynn
  • E. Reed
  • Q. Q. Li
Research Article

DOI: 10.1007/s00018-005-5017-3

Cite this article as:
Wang, G., Li, X., Huang, F. et al. CMLS, Cell. Mol. Life Sci. (2005) 62: 881. doi:10.1007/s00018-005-5017-3

Abstract.

β-Elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of β-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that β-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, β-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27kip1 and phospho-Cdc2 (Tyr-15). Moreover, β-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of β-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that β-elemene triggered apoptosis in NSCLC cells. Our results clearly show that β-elemene induced caspase-3, −7 and −9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of β-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

Key words.

Lung cancer NSCLC elemene cell cycle arrest G2-M arrest apoptosis 

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • G. Wang
    • 1
  • X. Li
    • 1
  • F. Huang
    • 1
  • J. Zhao
    • 1
  • H. Ding
    • 1
  • C. Cunningham
    • 1
  • J. E. Coad
    • 1
  • D. C. Flynn
    • 1
  • E. Reed
    • 1
  • Q. Q. Li
    • 1
  1. 1.The Mary Babb Randolph Cancer Center and the Department of Microbiology, Immunology and Cell BiologyWest Virginia University Health Sciences CenterMorgantownUSA

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