title: TGF-β1-induced epithelial-mesenchymal transition and acetylation of Smad2 and Smad3 are negatively regulated by EGCG in human A549 lung cancer cells.
abstract: 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.
authors: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
authors: Hyeonseok
authors: H
authors: Ko
authors: Youngsin
authors: Y
authors: So
authors: Hyelin
authors: H
authors: Jeon
authors: Mi-Hyeon
authors: MH
authors: Jeong
authors: Hyo-Kyoung
authors: HK
authors: Choi
authors: Seung-Hee
authors: SH
authors: Ryu
authors: Sang-Wook
authors: SW
authors: Lee
authors: Ho-Geun
authors: HG
authors: Yoon
authors: Kyung-Chul
authors: KC
authors: Choi
mesh_terms: D000107:Acetylation; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D002392:Catechin; C045651:epigallocatechin gallate; D050880:p300-CBP Transcription Factors