Abstract ▼ AI-Helper

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. Recent studies have revealed that the transcriptional coactivator p300/CBP may also play a role i...

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. Recent studies have revealed that the transcriptional coactivator p300/CBP may also play a role in TGF-β1/Smad signaling. In this study, I found that activation of p300/CBP, a histone acetyltransferase(HAT), by TGF-β1 mediates Epithelial?mesenchymal transition (EMT) via acetylating Smad2 and Smad3 in TGF-β1 signaling pathway. As suggested in recent reports, the development of a HAT inhibitor from natural compounds is a key step in the development of a novel therapeutic agent. Several natural dietary factors, such as garcinol, curcumin, anacardic acid, and epigallocatechin-3-gallate (EGCG), have the ability to inhibit HAT activity. I demonstrated that treatment with EGCG inhibited p300/CBP activity in human lung cancer cells. Also, I observed that EGCG potently inhibited TGF-β1-induced EMT and reversed the up-regulation of various genes during EMT. My 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.

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