Chidamide alleviates TGF-ß-induced epithelial-mesenchymal transition in lung cancer cell lines.
Mol Biol Rep
; 43(7): 687-95, 2016 Jul.
Article
em En
| MEDLINE
| ID: mdl-27188428
ABSTRACT
Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-ß-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-ß induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-ß-induced SMAD2 phosphorylation and attenuated TGF-ß-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-ß-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-ß-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-ß suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-ß-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
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Fator de Crescimento Transformador beta
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Inibidores de Histona Desacetilases
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Transição Epitelial-Mesenquimal
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Aminopiridinas
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Taiwan