title: MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells.
abstract: Histone deacetylase (HDAC) inhibitors have recently emerged as a new class of anti-cancer agents. Trichostatin A (TSA), a classical HDAC inhibitor, has been demonstrated to induce cell cycle arrest, promote cell apoptosis, and inhibit metastasis. However, the molecular mechanism underlying TSA function has not been fully elucidated. In the current study, we found that TSA treatment induced altered expression of cell cycle-associated genes in HCT116 cells by RT-PCR array. Among the 84 genes related to cell cycle control, 34 genes were significantly altered by TSA treatment, with 7 genes upregulated and 27 genes downregulated. Interestingly, gene expression of minichromosome maintenance protein-2 (MCM-2) was significantly downregulated by TSA treatment. This was confirmed by quantitative RT-PCR and Western blotting. Moreover, silencing of MCM-2 by siRNA led to cell cycle arrest and apoptosis in HCT116 cells. In addition, TSA caused an increase of phosphorylated JNK, which was involved in downregulation of MCM-2. Together, our results suggest that MCM-2 is a noval therapeutic target of TSA in colon cancer cells.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yangbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinging
authors.initials: X
authors.lastname: Guan
authors.forename: Xueli
authors.initials: X
authors.lastname: Pang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D064111:Minichromosome Maintenance Complex Component 2; D058990:Molecular Targeted Therapy / Q000379:methods*; D009687:Nuclear Proteins / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C012589:trichostatin A; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2
keywords: Apoptosis; Cell cycle; Colon cancer; MCM-2; TSA