Diet-Derived Gallated Catechins Prevent TGF-β-Mediated Epithelial-Mesenchymal Transition, Cell Migration and Vasculogenic Mimicry in Chemosensitive ES-2 Ovarian Cancer Cells

Abstract

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.

Aim: We assessed the effects of eight catechins on TGF-β-mediated cell migration and induction of EMT biomarkers, as well as on In Vitro vasculogenic mimicry (VM), 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.

Acknowledgments

BA holds an Institutional Research Chair in Cancer Prevention and Treatment. We thank Alain Zgheib for helpful technical assistance.

Disclosure Statement

The authors declare that they have no competing interests.

Additional information

Funding

This study was funded by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC).