Antiproliferative effect of β-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase

X. Li, Gangduo Wang, J. Zhao, H. Ding, C. Cunningham, F. Chen, D. C. Flynn, E. Reed, Q. Q. Li

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Elemene is a natural antitumor plant drug. However, the effect of elemene on cell growth in ovarian cancer is unknown. In this study, we show that β-elemene inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and their parental cells, but had only a marginal effect in human ovary cells, indicating differential inhibitory effects on cell growth between ovarian cancer cells and normal ovary cells. We also demonstrated for the first time that β-elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells compared to sensitive cells. In addition, cell cycle analysis revealed a synergistic effect of β-elemene and cisplatin on the induction of cell cycle G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45. Finally, the combination of β-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression.

Original languageEnglish (US)
Pages (from-to)894-904
Number of pages11
JournalCellular and Molecular Life Sciences
Volume62
Issue number7-8
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

G2 Phase
Cell Cycle Checkpoints
Cell Division
Cells
Carcinoma
Cisplatin
G2 Phase Cell Cycle Checkpoints
Ovarian Neoplasms
Cyclin B1
Cell growth
Growth
elemene
Ovary
Cell Cycle
Phosphorylation
Pharmaceutical Preparations
Antineoplastic Agents
Down-Regulation

Keywords

  • β-elemene
  • Cell cycle
  • Cisplatin
  • Drug resistance
  • G2-M arrest
  • Ovarian cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Antiproliferative effect of β-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. / Li, X.; Wang, Gangduo; Zhao, J.; Ding, H.; Cunningham, C.; Chen, F.; Flynn, D. C.; Reed, E.; Li, Q. Q.

In: Cellular and Molecular Life Sciences, Vol. 62, No. 7-8, 04.2005, p. 894-904.

Research output: Contribution to journalArticle

Li, X. ; Wang, Gangduo ; Zhao, J. ; Ding, H. ; Cunningham, C. ; Chen, F. ; Flynn, D. C. ; Reed, E. ; Li, Q. Q. / Antiproliferative effect of β-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. In: Cellular and Molecular Life Sciences. 2005 ; Vol. 62, No. 7-8. pp. 894-904.
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abstract = "Elemene is a natural antitumor plant drug. However, the effect of elemene on cell growth in ovarian cancer is unknown. In this study, we show that β-elemene inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and their parental cells, but had only a marginal effect in human ovary cells, indicating differential inhibitory effects on cell growth between ovarian cancer cells and normal ovary cells. We also demonstrated for the first time that β-elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells compared to sensitive cells. In addition, cell cycle analysis revealed a synergistic effect of β-elemene and cisplatin on the induction of cell cycle G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45. Finally, the combination of β-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression.",
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