A novel anti‑cancer effect of resveratrol: reversal of epithelial‑mesenchymal transition in prostate cancer cells

Mol Med Rep. 2014 Oct;10(4):1717-24. doi: 10.3892/mmr.2014.2417. Epub 2014 Jul 23.

Abstract

Carcinoma progression is associated with the loss of epithelial features and the acquisition of a mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT). Resveratrol, a natural polyphenolic compound found in grapes, berries and peanuts, has a wide range of pharmacological properties, including anti-tumor metastasis properties. The underlying mechanism through which resveratrol inhibits metastasis of prostate cancer (PCa) is not yet fully understood; however, it is thought to be associated with the disruption of EMT. In the present study, lipopolysaccharide (LPS) was used to trigger EMT in PC-3 and LNCaP PCa cell lines, and the cell lines were subsequently treated with resveratrol. The results demonstrated that exposure of PC-3 and LNCaP cells to LPS resulted in morphological alterations characteristic of EMT, as well as an increase in the expression of the mesenchymal marker vimentin and a decrease in the expression of E‑cadherin. In addition, LPS exposure resulted in an increase in cell motility, along with an upregulation of the transcription factor glioma-associated oncogene homolog 1 (Gli1). However, treatment with resveratrol inhibited LPS-induced morphological changes, decreased the expression of LPS-induced markers of EMT and inhibited the expression of Gli1, resulting in the inhibition of in vitro cell motility and invasiveness. These results provide a novel perspective for the anti-invasion mechanism of resveratrol, suggesting that the effect is in part due to its ability to inhibit the EMT process through the Hedgehog signaling pathway.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Hedgehog Proteins / metabolism
  • Humans
  • Lipopolysaccharides / toxicity
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vimentin / genetics
  • Vimentin / metabolism
  • Zinc Finger Protein GLI1

Substances

  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • GLI1 protein, human
  • Hedgehog Proteins
  • Lipopolysaccharides
  • RNA, Messenger
  • Stilbenes
  • Transcription Factors
  • Vimentin
  • Zinc Finger Protein GLI1
  • Resveratrol