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

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.

► We show that EGF promotes epithelial–mesenchymal transition in the MCF-7 breast cancer cell line. ► The phenotypic effects are accompanied by enhanced migration and upregulation of mesenchymal markers. ► Resveratrol is able to inhibit EGF-induced EMT process in MCF-7 cells. ► Inhibition of ERK 1/2 activation by resveratrol is critical to block EMT modifications. ► These findings can support a possible role for resveratrol in the chemoprevention of invasive carcinomas.