Inhibition of histone deacetylase activity is a novel function of the antifolate drug methotrexate

Pei Ming Yang, Jung Hsin Lin, Wen Yu Huang, Yi Chu Lin, Shu Hao Yeh, Ching Chow Chen

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)1396-1399
頁數4
期刊Biochemical and Biophysical Research Communications
391
發行號3
DOIs
出版狀態已發佈 - 1月 15 2010
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 生物物理學
  • 細胞生物學
  • 分子生物學

指紋

深入研究「Inhibition of histone deacetylase activity is a novel function of the antifolate drug methotrexate」主題。共同形成了獨特的指紋。

引用此