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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yang PM,Lin JH,Huang WY,Lin YC,Yeh SH,Chen CC

doi

10.1016/j.bbrc.2009.12.072

subject

Has Abstract

pub_date

2010-01-15 00:00:00

pages

1396-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)02445-0

journal_volume

391

pub_type

杂志文章

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