Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors

PLoS One. 2013;8(3):e58719. doi: 10.1371/journal.pone.0058719. Epub 2013 Mar 14.

Abstract

Epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / pathology*
  • Cell Movement / drug effects
  • Down-Regulation / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • MCF-7 Cells
  • Neoplasm Invasiveness
  • Phenotype
  • Phosphorylation / drug effects
  • Sesquiterpenes / pharmacology*
  • Transcription Factors / genetics*
  • Transforming Growth Factor beta1 / pharmacology
  • Up-Regulation / drug effects
  • snRNP Core Proteins / genetics
  • snRNP Core Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • SNRPD3 protein, human
  • Sesquiterpenes
  • Transcription Factors
  • Transforming Growth Factor beta1
  • beta-elemene
  • snRNP Core Proteins

Grants and funding

The authors have no support or funding to report.