Discovery of polyoxometalate-based HDAC inhibitors with profound anticancer activity in vitro and in vivo

被引：66

作者：

Dong, Zhixiong ^{[1
]}

Tan, Ruikang ^{[2
]}

Cao, Jian ^{[3
]}

Yang, Yang ^{[1
]}

Kong, Chenfei ^{[1
]}

Du, Juan ^{[1
]}

Zhu, Shan ^{[1
]}

Zhang, Yu ^{[1
]}

Lu, Jun ^{[1
]}

Huang, Baiqu ^{[1
]}

Liu, Shuxia ^{[2
]}

机构：

[1] NE Normal Univ, Inst Cytol & Genet, Minist Educ, Key Lab Mol Epigenet, Changchun 130024, Peoples R China

[2] NE Normal Univ, Coll Chem, Minist Educ, Key Lab Polyoxometalates Sci, Changchun 130024, Peoples R China

[3] Jilin Univ, China Japan Union Hosp, Changchun 130023, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 06期

基金：

美国国家科学基金会;

关键词：

Polyoxometalate; Histone deacetylase; HDACI; Anticancer effect; HISTONE DEACETYLASE INHIBITOR; P21/WAF1/CIP1 GENE PROMOTER; ANTITUMOR-ACTIVITY; CANCER-CELLS; ACTIVATION; POLYOXOMOLYBDATE; REPRESSES; ASSAY; SP1; TRICHOSTATIN;

D O I：

10.1016/j.ejmech.2011.03.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We obtained 5 positive novel histone deacetylase inhibitors (HDACIs) from a polyoxometalate (POM) library by using a cell-based screening system targeting the p21 gene promoter. Among them, PAC-320, a new tri-organic-tin-substitute germanotungstate, displayed remarkable extracellular inhibitory activity. Meanwhile, the crystal structure of PAC-320 was characterized by X-ray crystallography. PAC-320 could stably exist under physiological conditions as revealed by UV spectrum, CV and TG. PAC-320 possessed a strong inhibitory effect to intracellular HDAC activity. More significantly, PAC-320 inhibited the growth of a variety of cancer cells, and exhibited remarkable anticancer effect in a hepatocarcinoma H22 cell mice model. This study revealed, for the first time, that the HDAC inhibitory activity is a mechanism by which POMs exert their anticancer effect. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：2477 / 2484

页数：8

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