title: The histone deacetylase inhibitor trichostatin A induces cell cycle             arrest and apoptosis in colorectal cancer cells via p53-dependent and -independent             pathways.
abstract: Many chemotherapeutic agents induce apoptosis via a p53-dependent pathway.             However, up to 50% of human cancers have p53 mutation and loss of p53 function.             Histone deacetylase inhibitors (HDACIs) are emerging as a potentially important             new class of anticancer agents. Here, we report that, Trichostatin A (TSA), a             pan-HDAC inhibitor, could induce G2/M cell cycle arrest and apoptosis in both             colorectal cancer cell lines with wild-type p53 (HT116 cells) and mutant p53 (HT29             cells), although HCT116 cells had more apoptotic cells than HT29 cells. TSA induces             apoptosis in both cell lines via the mitochondrial pathway as indicated by decrease             of the mitochondrial membrane potential (MMP) and activation of caspase-3. Additionally,             TSA induces expression of the pro-apoptotic protein Bax and decreases the expression             of the anti-apoptotic proteins Bcl-2 and Bcl-xL in both cell lines. Bax knockdown             by siRNA significantly impaired TSA-induced apoptosis in both cell lines. These             data suggest that TSA induces G2/M cell cycle arrest and Bax-dependent apoptosis             in colorectal cancer cells (HCT116 cells and HT29 cells) by both p53-dependent             and -independent mechanisms. However, cells with normal p53 function are more             sensitive to TSA-induced apoptosis.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Zhang
authors.forename: Chun-Xiang
authors.initials: CX
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Mei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015179:Colorectal Neoplasms; D004789:Enzyme Activation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D045325:HCT116 Cells; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009154:Mutation; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C012589:trichostatin A; C505407:CASP3 protein, human; D053148:Caspase 3