期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 385, 期 1, 页码 16-21出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.05.022
关键词
Hypoxia; HlF-1 alpha inhibitor; Benzimidazole; Angiogenesis; Hsp90; Akt
资金
- KRIBB Research Initiative Program, South Korea
- Korea Science and Engineering Foundation (KOSEF) grants [(2008-05676, RO1-2008000-11354-0]
- Ministry of Science and Technology, South Korea
- National Research Foundation of Korea [2008-05676] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hypoxia-inducible factor (HIF)-1 is a therapeutic target in solid tumors. We report the novel benzimidazole analogue AC1-004, obtained from a chemical library using an HRE-dependent cell-based assay in colorectal carcinoma HCT-116 cells. The accumulation of hypoxia-induced HIF-1 alpha was inhibited by compound AC1-004 in various cancer cells, including HCT-116, MDA-MB435, SK-HEP1, and Caki-1. Further, AC1-004 down-regulated VEGF and EPO, target genes of HIF-1, and inhibited in vitro tube formation of HUVEC, suggesting its potential inhibitory activity on angiogenesis. Importantly. AC1-004 was found to regulate the stability of HIF-1 alpha through the Hsp90-Akt pathway, leading to the degradation of HIF-1 alpha. An in vivo antitumor study demonstrated that AC1-004 reduced tumor size significantly (i.e., by 58.6%), without severe side effects. These results suggest the benzimidazole analogue AC1-004 is a novel HIF inhibitor that targets HIF-1 alpha via the Hsp90-Akt pathway, and that it can be used as a new lead in developing anticancer drugs. (C) 2009 Elsevier Inc. All rights reserved
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据