Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis

Toxicology. 2013 Jan 7;303:139-46. doi: 10.1016/j.tox.2012.09.017. Epub 2012 Nov 9.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which in turn promotes carcinoma invasion and metastasis. Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenolic compound found in grapes, red wine and several other plants. Numerous reports in the literature indicate that resveratrol can suppress cancer invasion and metastasis. However, the underlying mechanisms of inhibiting metastasis by resveratrol are complex, not fully elucidated and the subject of intense scientific debate. Despite evidence indicating that EMT can be a target for resveratrol, little is known about the effect of resveratrol on lung cancer cells. Our previous studies demonstrated that TGF-β1 induces EMT to promote lung adenocarcinoma invasion and metastasis. To understand the repressive role of resveratrol in lung cancer invasion and metastasis, we sought to investigate the potential use of resveratrol as an inhibitor of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here we show that when A549 cells are treated with TGF-β1 and resveratrol, the latter inhibits the initiation of TGF-β1-induced EMT. Our results show that 20 μM resveratrol increases expression of the epithelial phenotype marker E-cadherin and represses the expression of the mesenchymal phenotype markers, Fibronectin and Vimentin during the initiation of TGF-β1-induced EMT. Resveratrol also inhibits expression of EMT-inducing transcription factors Snail1 and Slug, although the expression of the Twist1 transcription factor remained unchanged. Resveratrol inhibits the TGF-β1-induced increase in cell adhesion, migration and invasion of A549 lung cancer cells. Taken together, our findings provide new evidence that resveratrol suppresses lung cancer invasion and metastasis in vitro through inhibiting TGF-β1-induced EMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cadherins / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Fibronectins / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Transforming Growth Factor beta1 / pharmacology
  • Vimentin / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • Fibronectins
  • Stilbenes
  • Transforming Growth Factor beta1
  • Vimentin
  • Resveratrol