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Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity.

Abstract：

:Hypoxia is generally detected in central regions of solid tumors and regulates a variety of transcription factors including hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a pivotal role in cellular response to low oxygen concentration, such as angiogenesis in tumor. Here, we found that a histone deacetylase (HDAC) inhibitor, FK228, inhibits the induction and activity of HIF-1 in response to hypoxia. Moreover, FK228 significantly suppressed the induction of vascular endothelial growth factor (VEGF) under hypoxia, suggesting that FK228 contributes to the inhibition of tumor angiogenesis. In Lewis lung carcinoma model, FK228 also blocked angiogenesis induced by hypoxia. These results suggest that FK228 can downregulate hypoxia-responsive angiogenesis through suppression of HIF-1alpha activity.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Mie Lee Y,Kim SH,Kim HS,Jin Son M,Nakajima H,Jeong Kwon H,Kim KW

doi

10.1016/s0006-291x(02)02787-0

subject

Has Abstract

pub_date

2003-01-03 00:00:00

pages

241-6

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X02027870

journal_volume

300

pub_type

杂志文章

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