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 output: Contribution to journalArticle

197 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)881-893
Number of pages13
JournalCellular and Molecular Life Sciences
Volume62
Issue number7-8
DOIs
StatePublished - Apr 1 2005

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Elemene
  • G2-M arrest
  • Lung cancer
  • NSCLC

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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