| Literature DB >> 20026300 |
Pei-Ming Yang1, Jung-Hsin Lin, Wen-Yu Huang, Yi-Chu Lin, Shu-Hao Yeh, Ching-Chow Chen.
Abstract
Methotrexate (MTX) is a dihydrofolate reductase (DHFR) inhibitor widely used for treating human cancers, and overexpression of histone deacetylase (HDAC) is usually found in tumors. HDAC inhibitors (HDACi) can reactivate tumor suppressor genes and serve as potential anti-cancer drugs. In this study, we found that MTX shared structural similarity with some HDACi and molecular modeling showed that MTX indeed docks into the active site of HDLP, a bacterial homologue of HDAC. Subsequent in vitro assay demonstrated MTX's inhibition on HDAC activity in human cancer cells. The global acetylation of histone H3 was also induced by MTX. Moreover, MTX inhibited immunoprecipitated HDAC1/2 activity but not their protein levels. This study provides evidence that MTX inhibits HDAC activity. Copyright 2009 Elsevier Inc. All rights reserved.Entities:
Mesh：
Substances：
Year: 2009 PMID： 20026300 DOI： 10.1016/j.bbrc.2009.12.072
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575