TGF-β1-induced epithelial–mesenchymal transition and acetylation of Smad2 and Smad3 are negatively regulated by EGCG in Human A549 lung cancer cells

Transforming growth factor-β1, the key ligand of Smad-dependent signaling pathway, is critical for epithelial–mesenchymal transition during embryo-morphogenesis, fibrotic diseases, and tumor metastasis. In this study, we found that activation of p300/CBP, a histone acetyltransferase, by TGF-β1 mediates Epithelial–mesenchymal transition (EMT) via acetylating Smad2 and Smad3 in TGF-β1 signaling pathway. We demonstrated that treatment with EGCG inhibited p300/CBP activity in human lung cancer cells. Also, we observed that EGCG potently inhibited TGF-β1-induced EMT and reversed the up-regulation of various genes during EMT. Our findings suggest that EGCG inhibits the induction of p300/CBP activity by TGF-β1. Therefore, EGCG inhibits TGF-β1-mediated EMT by suppressing the acetylation of Smad2 and Smad3 in human lung cancer cells.

► EGCG inhibited acetylation of Smad2 and Smad3 by p300/CBP during TGF-b1-induced EMT, and EGCG is a strong HAT inhibitor.
► EGCG suppressed the TGF-b1-induced EMT related genes.
► EGCG antagonizes the migration of human lung cancer cells permitted by TGF-b1-induced EMT.
► EGCG is directly prevented EMT and blocked invasion and metastasis of cancer cells.