Inhibition of hypoxia-induced angiogenesis by sodium butyrate, a histone deacetylase inhibitor, through hypoxia-inducible factor-1alpha suppression.
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.
Kim
Se-Hee
SH
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Kyu-Won
KW
Jeong
Joo-Won
JW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D015536:Down-Regulation; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020533:Angiogenesis Inhibitors; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D012964:Sodium