Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells

Daniele Vergara; Concetta Maria Valente; Andrea Tinelli; Carlo Siciliano; Vito Lorusso; Raffaele Acierno; Giovanna Giovinazzo; Angelo Santino; Carlo Storelli; Michele Maffia

doi:10.1016/j.canlet.2011.04.009

Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells

Cancer Lett. 2011 Nov 1;310(1):1-8. doi: 10.1016/j.canlet.2011.04.009. Epub 2011 Jun 24.

Authors

Daniele Vergara¹, Concetta Maria Valente, Andrea Tinelli, Carlo Siciliano, Vito Lorusso, Raffaele Acierno, Giovanna Giovinazzo, Angelo Santino, Carlo Storelli, Michele Maffia

Affiliation

¹ Laboratory of General Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 73100, Lecce, Italy.

PMID: 21794976
DOI: 10.1016/j.canlet.2011.04.009

Abstract

Carcinoma progression is associated with the loss of epithelial features, and the acquisition of a mesenchymal phenotype by tumour cells. Herein we show that exposure of MCF-7 cells to epidermal growth factor (EGF) resulted in morphological alterations characteristic of epithelial-to-mesenchymal transition (EMT). EGF treatment resulted in increased motility along with an up-regulation of transcription factors Slug, Zeb1, Zeb2, and mesenchymal markers Vimentin and N-cadherin. Treatment of MCF-7 cells with a combined stimulation of EGF and resveratrol, a naturally occurring stilbene with antitumor properties, failed to alter cell morphology, motility and overexpression of EMT markers induced by EGF. Using specific chemical inhibitors, we demonstrated that EGF-induced EMT is mediated by extracellular signal-regulated kinase 1/2 (ERK 1/2) signalling pathway and that resveratrol is able to repress EGF-induced ERK activation. In summary, these data provide new evidence of the inhibitory effect of resveratrol on EGF-induced EMT cell transformation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actin Depolymerizing Factors / metabolism
Angiogenesis Inhibitors / pharmacology
Breast Neoplasms / genetics
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Butadienes / pharmacology
Cadherins / genetics
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects*
Cell Shape / drug effects
Cell Survival / drug effects
Enzyme Inhibitors / pharmacology
Epidermal Growth Factor / pharmacology*
Epithelial-Mesenchymal Transition / drug effects*
Epithelial-Mesenchymal Transition / genetics
Gene Expression Regulation, Neoplastic / drug effects
Homeodomain Proteins / genetics
Humans
Immunoblotting
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism
Nitriles / pharmacology
Phosphorylation / drug effects
Repressor Proteins / genetics
Resveratrol
Reverse Transcriptase Polymerase Chain Reaction
Snail Family Transcription Factors
Stilbenes / pharmacology*
Transcription Factors / genetics
Vimentin / genetics
Zinc Finger E-box Binding Homeobox 2
Zinc Finger E-box-Binding Homeobox 1

Substances

Actin Depolymerizing Factors
Angiogenesis Inhibitors
Butadienes
Cadherins
Enzyme Inhibitors
Homeodomain Proteins
Nitriles
Repressor Proteins
SNAI1 protein, human
Snail Family Transcription Factors
Stilbenes
Transcription Factors
U 0126
Vimentin
ZEB1 protein, human
ZEB2 protein, human
Zinc Finger E-box Binding Homeobox 2
Zinc Finger E-box-Binding Homeobox 1
Epidermal Growth Factor
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Resveratrol