Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest.
Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest.
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DOI：
10.1248/bpb.28.849
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发表时间：
2005-05
影响因子：
2
通讯作者：
Taishi Maeda;Y. Nagaoka;Y. Kawai;Nobumasa Takagaki;C. Yasuda;Shingo Yogosawa;Y. Sowa;T. Sakai;S. Uesato
中科院分区：
文献类型：
--
作者：
Taishi Maeda;Y. Nagaoka;Y. Kawai;Nobumasa Takagaki;C. Yasuda;Shingo Yogosawa;Y. Sowa;T. Sakai;S. Uesato
合成了两种化合物，它们具有不同于我们新系列组蛋白脱乙酰酶（HDAC）抑制剂的结构成分，以确定结构-活性关系。还检查了HDAC抑制剂对癌细胞增殖的抑制作用是否与其他HDAC抑制剂一样涉及p53突变的MG 63人骨肉瘤细胞中的p21/WAF 1诱导和G（1）或G（2）/M停滞。结果表明，分子两端含有2-萘羰基和异羟肟酸，分子中心含有亚苯基的抑制剂通过刺激p21/WAF 1基因启动子活性，显著诱导p21/WAF 1蛋白的表达。细胞周期分析显示，这些化合物可使MG 63细胞阻滞于G（2）/M期。
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.