Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Inhibitory Effects of Cancer Cell Proliferation by Novel Histone Deacetylase Inhibitors Involve p21/WAF1 Induction and G2/M Arrest
Taishi MaedaYasuo NagaokaYuki KawaiNobumasa TakagakiChikako YasudaShingo YogosawaYoshihiro SowaToshiyuki SakaiShinichi Uesato
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2005 Volume 28 Issue 5 Pages 849-853

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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 G1 or G2/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 G2/M phase.

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© 2005 The Pharmaceutical Society of Japan
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