Inhibition of hypoxia-induced angiogenesis by sodium butyrate, a histone deacetylase inhibitor, through hypoxia-inducible factor-1alpha suppression

Oncol Rep. 2007 Apr;17(4):793-7.

Abstract

Hypoxia-inducible factor-1 (HIF-1) plays a pivotal role in cellular response to low oxygen concentration, such as angiogenesis in tumors. Here, we found that a histone deacetylase inhibitor, sodium butyrate, inhibits the hypoxia-induced induction and activity of HIF-1alpha in HT1080 human fibrosarcoma cells. Moreover, sodium butyrate also suppressed the hypoxia-stimulated angiogenic effects and downregulated HIF-1alpha and vascular endothelial growth factor expression in vascular endothelial cells. These findings suggest that sodium butyrate may play important roles in tumor suppression via inhibition of HIF-1alpha mediated angiogenesis under hypoxic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Aryl Hydrocarbon Receptor Nuclear Translocator / antagonists & inhibitors*
  • Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
  • Butyrates / pharmacology*
  • Down-Regulation
  • Gene Expression
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hypoxia / metabolism
  • Neoplasms / blood supply*
  • Neovascularization, Pathologic / metabolism*
  • Sodium / pharmacology
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Angiogenesis Inhibitors
  • Butyrates
  • Histone Deacetylase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Sodium