Chidamide alleviates TGF-[beta]-induced epithelial-mesenchymal transition in lung cancer cell lines

• Published in: Molecular biology reports 2016-07, Vol.43 (7), p.687
• Main Authors: Lin, Sheng-hao, Wang, Bing-yen, Lin, Ching-hsiung, Chien, Peng-ju, Wu, Yueh-feng, Ko, Jiunn-liang, Chen, Jeremy J, W
• Format: Article
• Language: English
• Subjects: Growth factors; Lung cancer; Metastasis; Molecular biology; Phosphorylation; Polymerase chain reaction
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-016-4005-z

Transforming growth factor-[beta] (TGF-[beta])-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-[beta]-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-[beta] 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-[beta]-induced SMAD2 phosphorylation and attenuated TGF-[beta]-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-[beta]-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-[beta]-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-[beta] suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-[beta]-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.