title: HDAC inhibitors induce epithelial-mesenchymal transition in colon carcinoma cells.
abstract: The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various types of cancers. We investigated the EMT phenotype in four colon cancer cell lines when challenged with HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) with or without transforming growth factor-β1 (TGF-β1) treatment. Four colon cancer cell lines with different phenotypes in regards to tumorigenicity, microsatellite stability and DNA mutation were used. EMT phenotypes were assessed by the expression of E-cadherin and vimentin using western blot analysis, immunofluorescence, quantitative real-time RT-PCR following treatment with TSA (100 or 200 nM) or VPA (0.5 mM) with or without TGF-β1 (5 ng/ml) for 24 h. Biological EMT phenotypes were also evaluated by cell morphology, migration and invasion assays. TSA or VPA induced mesenchymal features in the colon carcinoma cells by a decrease in E-cadherin and an increase in vimentin expression at the mRNA and protein levels. Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of vimentin. These responses occurred after 6 h and increased until 24 h. Colon cancer cells changed from a round or rectangular shape to a spindle shape with increased migration and invasion ability following TSA or VPA treatment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). TSA or VPA induced a mesenchymal phenotype in the colon carcinoma cells and these effects were augmented in the presence of TGF-β1. HDAC inhibitors require careful caution before their application as new anticancer drugs for colon cancers.
authors: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Meiying
authors: M
authors: Ji
authors: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Eun Jeoung
authors: EJ
authors: Lee
authors: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Ki Bae
authors: KB
authors: Kim
authors: Department of Physiology, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Yangmi
authors: Y
authors: Kim
authors: Department of Pathology, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Rohyun
authors: R
authors: Sung
authors: Department of General Surgery, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Sang-Jeon
authors: SJ
authors: Lee
authors: Department of Orthopedic Surgery, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Don Soo
authors: DS
authors: Kim
authors: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 361-711, Republic of Korea.
authors: Seon Mee
authors: SM
authors: Park
mesh_terms: D015820:Cadherins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D045325:HCT116 Cells; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*; D014746:Vimentin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C012589:trichostatin A; D014635:Valproic Acid