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

You Mie Lee, Se Hee Kim, Hae Sun Kim, Myung Jin Son, Hidenori Nakajima, Ho Jeong Kwon, Kyu Won Kim

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147 Citations (Scopus)

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-1α activity.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume300
Issue number1
DOIs
Publication statusPublished - 2003

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Health 21 R&D Project (HMP-01-PJ1-PG1-01CH04-0005), Ministry of Health and Welfare, Korea.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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