标题:Discovery of N-hydroxy-4-(3-phenylpropanamido)benzamide derivative 5j, a novel histone deacetylase inhibitor, as a potential therapeutic agent for human breast cancer.
作者:Feng J;Fang H;Wang X;Jia Y;Zhang L;Jiao J;Zhang J;Gu L;Xu W
作者机构:[Feng, J] Institute of Medicinal Chemistry, Shandong University, Jinan, Shandong, China;[ Fang, H] Institute of Medicinal Chemistry, Shandong Universi 更多
通讯作者:Xu, WF
通讯作者地址:[Xu, WF]Shandong Univ, Sch Life Sci, Inst Med Chem, Jinan 250100, Shandong, Peoples R China.
来源:Cancer biology & therapy
出版年:2011
卷:11
期:5
页码:477-489
DOI:10.4161/cbt.11.5.14529
关键词:HDAC inhibitor; breast cancer; apoptosis; MMP-2; invasion
摘要:A novel series of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives comprising N-hydroxybenzamide group as zinc-chelating moiety were designed, synthesized and evaluated as histone deacetylases inhibitors. The thiophene substituted derivative 5j exhibited the best HDAC inhibition activity among these compounds. The present study was designed to evaluate the efficacy of 5j as a candidate compound for cancer therapy. Our results indicated that 5j exhibited better HDAC1, 8 and hela nuclear extract inhibition activities than SAHA, and good antiproliferative activities against a broad spectrum of human cancer cell lines especially for breast cancer. 5j induced cell cycle arrest at G(2)/M phase, and eventual apoptosis possibly by modulating p21, caspase-3 and Bcl-x(L) on MDA-MB-231 cells. In addition, 5j down regulated the active form of MMP2, and inhibited the invasion of MDA-MB-231 cell lines. Moreover, 5j significantly delayed the growth of MDA-MB-231 xenografts in mice after 3 weeks of peritoneal injection. In summary, our results suggest that 5j might have therapeutic potential for the treatment of human breast cancer.
收录类别:SCOPUS;SCIE
WOS核心被引频次:9
Scopus被引频次:9
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-79952357878&doi=10.4161%2fcbt.11.5.14529&partnerID=40&md5=c89af92030ef0184508dd759f95b116d
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