title: Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest.
abstract: Two compounds were synthesized which have a structural component other than those of our new series histone deacetylase (HDAC) inhibitors to determine the structure-activity relationship. It was also examined whether the inhibitory effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1 induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2-naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the phenylene component at the center of molecule markedly induce the p21/WAF1 protein by stimulating p21/WAF1 gene promoter activity. Furthermore, cell cycle analysis revealed that these compounds arrest MG63 cells in the G(2)/M phase.
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Maeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nagaoka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawai
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Takagaki
authors.forename: Chikako
authors.initials: C
authors.lastname: Yasuda
authors.forename: Shingo
authors.initials: S
authors.lastname: Yogosawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
mesh_terms: D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases