https://scholars.lib.ntu.edu.tw/handle/123456789/560411
標題: | Inhibition of histone deacetylase activity is a novel function of the antifolate drug methotrexate | 作者: | Yang P.-M. Lin J.-H. Huang W.-Y. Lin Y.-C. Yeh S.-H. CHING-CHOW CHEN |
關鍵字: | Acetylation; Histone deacetylase; Histone deacetylase inhibitor; Methotrexate | 公開日期: | 2010 | 卷: | 391 | 期: | 3 | 起(迄)頁: | 1396-1399 | 來源出版物: | Biochemical and Biophysical Research Communications | 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. ? 2009 Elsevier Inc. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560411 | ISSN: | 0006291X | DOI: | 10.1016/j.bbrc.2009.12.072 | SDG/關鍵字: | histone deacetylase; histone deacetylase 1; histone deacetylase 2; histone deacetylase like protein; histone H3; methotrexate; unclassified drug; acetylation; article; cancer cell; controlled study; drug binding; drug structure; enzyme activity; enzyme assay; enzyme inhibition; female; human; human cell; immunoprecipitation; in vitro study; molecular docking; molecular model; priority journal; structure analysis; Antimetabolites, Antineoplastic; Cell Line, Tumor; Folic Acid Antagonists; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Methotrexate; Bacteria (microorganisms) |
顯示於: | 藥理學科所 |
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