title: Trichostatin A induces mesenchymal-like morphological change and gene expression but inhibits migration and colony formation in human cancer cells.
abstract: Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl from lysine residues in histones and other proteins, which results in gene transcriptional repression and subsequent changes in signaling events. HDACs inhibitors (HDACIs) have been used to reverse the aberrant epigenetic changes associated with cancer. However, the effects of HDACIs on epithelial-mesenchymal transition (EMT) in human cancer cells remain unclear. EMT is a fundamental process governing morphogenesis in multicellular organisms and promotes cancer invasion and metastasis. In this study, human cancer cells were treated with the HDACI trichostatin A (TSA). TSA was found to induce mesenchymal‑like morphological changes in BGC-823 human gastric cancer and MCF-7 breast cancer cells, and increase the expression levels of the mesenchymal markers Vimentin and Twist. However, the expression levels of the epithelial cell marker E-cadherin were also increased in response to TSA treatment, while cell migration was reduced by TSA. Furthermore, TSA decreased cancer cell colony formation in BGC-823 and MCF-7 cells, and led to the deregulation of β-catenin, a critical signaling molecule involved in EMT. In conclusion, the results suggested that TSA exhibits dual functions in EMT induction and inhibition in human cancer cells, but the detailed mechanisms require further investigation.
authors.affiliation: Department of Biochemistry, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Rong-Fei
authors.initials: RF
authors.lastname: Han
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Zi-Shan
authors.initials: ZS
authors.lastname: Yang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Chen
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Wan-Cai
authors.initials: WC
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin; C012589:trichostatin A; D006655:Histone Deacetylases