Diet‐derived gallated catechins prevent TGF‐b‐mediated epithelial‐mesenchymal transition, cell migration and vasculogenic mimicry in chemosensitive ES‐2 ovarian cancer cells

Background Transforming growth factor (TGF)‐β triggers ovarian cancer metastasis through epithelial‐mesenchymal transition (EMT). Whereas drug design strategies targeting the TGF‐β signaling pathway have been envisioned, the anti‐TGF structure:function aspect of chemopreventive diet‐derived catechins remains unexplored. Methods We assessed the effects of eight catechins on TGF‐β‐mediated cell migration using real‐time exCELLigence, induction of EMT biomarkers by RT‐qPCR and immunoblotting, and in vitro vasculogenic mimicry (VM) by 3D‐Matrigel cultures, a process partly regulated by EMT‐related transcription factors. Results TGF‐β‐mediated phosphorylation of Smad‐3 and p38 signaling intermediates was more effective in a chemosensitive ES‐2 ovarian cancer cell line but was inoperative in cis‐platinum‐ and adriamycin‐chemoresistant SKOV‐3 ovarian cancer cells. Increases in cell migration and in gene/protein expression of EMT biomarkers Fibronectin, Snail, and Slug were observed in ES‐2 cells. When VM was assessed in ES‐2 cells, 3D capillary‐like structures were formed and increases in EMT biomarkers found. Catechins bearing the galloyl moiety (CG, ECG, GCG, and EGCG) exerted potent inhibition of TGF‐β‐induced cell migration as well as EMT, and inhibited VM, in part through inhibition of Snail and matrix metalloproteinase‐2 secretion. Conclusions Our data suggest that diet‐derived catechins exhibit chemopreventive properties that circumvent the TGF‐β‐mediated signaling which contributes to the ovarian cancer metastatic phenotype. Support or Funding Information UQAM Foundation and Chaire in Cancer Prevention and Treatment