Sensitization of lung cancer cells to cisplatin by β-elemene is mediated through blockade of cell cycle progression: Antitumor efficacies of β-elemene and its synthetic analogs

Q. Quentin Li, Gangduo Wang, Furong Huang, Jueli M. Li, Christopher F. Cuff, Eddie Reed

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The development of effective agents for overcoming platinum chemoresistance in lung carcinoma continues to have high priority. We have demonstrated recently that β-elemene, a novel antitumor compound, enhances cisplatin activity by triggering lung cancer cell death via apoptosis. Here, we investigated whether β-elemene acts synergistically with cisplatin to inhibit non-small cell lung cancer (NSCLC) cell proliferation by blocking cell cycle progression. β-Elemene substantially increased the suppressive effect of cisplatin on cell growth and proliferation in the NSCLC cell lines H460 and A549. Furthermore, β-elemene augmented cisplatin in the cell cycle arrest of NSCLC cells at G2/M. This was associated with upregulated checkpoint kinase (CHK2) expression and reduced CDC2 activity (i.e., increased phosphorylation of CDC2 on Tyr-15 and decreased phosphorylation of CDC2 on Thr-161). Moreover, β-elemene and cisplatin in combination clearly decreased the protein levels of cyclin B1 and CDC25C and increased the levels of p21Cip1/Waf1, p27Kip1, and GADD45 in these cells, compared with the effects of either agent alone at the same concentration. These results suggest that the β-elemene-enhanced inhibitory effect of cisplatin on lung carcinoma cell proliferation is regulated by a CHK2-mediated CDC25C/CDC2/cyclin B1 signaling pathway and leads to the blockade of cell cycle progression at G2/M. A comparison of the cytotoxic efficacies of β-elemene and three synthetic analogs (β-elemenol, β-elemenal, and β-elemene fluoride) in the two lung cancer cell lines revealed that β-elemenol and β-elemene fluoride had the same antitumor efficacy as β-elemene, whereas β-elemenal was appreciably more potent than β-elemene. Thus, although all three synthetic analogs of β-elemene considerably suppressed NSCLC cell growth and proliferation, β-elemenal may have greater potential as an anticancer alternative to β-elemene in treating lung cancer and other tumors.

Original languageEnglish (US)
Article number488
JournalMedical Oncology
Volume30
Issue number1
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • Cell cycle arrest
  • Chinese medicine
  • Cisplatin resistance
  • Lung cancer
  • Synthetic analogs
  • β-Elemene

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Sensitization of lung cancer cells to cisplatin by β-elemene is mediated through blockade of cell cycle progression: Antitumor efficacies of β-elemene and its synthetic analogs'. Together they form a unique fingerprint.

  • Cite this