Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest.
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.
Maeda
Taishi
T
Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680, Japan.
Nagaoka
Yasuo
Y
Kawai
Yuki
Y
Takagaki
Nobumasa
N
Yasuda
Chikako
C
Yogosawa
Shingo
S
Sowa
Yoshihiro
Y
Sakai
Toshiyuki
T
Uesato
Shinichi
S
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
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases