Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1 alpha-p300 interaction by a small molecule

Abstract

Vascular endothelial growth factor (VEGF) plays a pro-angiogenic role in tumor progression. Stabilization of a key regulator termed the hypoxia inducible factor (HIF)-1 alpha under oxygen deficient environment around tumor is known to elicit expression of VEGF through binding to p300. Thus, inhibition of the HIF-1 alpha-p300 interaction would lead to down-regulation of VEGF expression, thereby providing potential cancer therapeutics. Here, we have screened a chemical library against the interaction of the HIF-1 alpha-derived peptide with p300 employing a fluorescence polarization-based assay. We have identified a compound as the most prominent inhibitor against the protein-protein interaction. Further, we have observed suppression of the mRNA level of VEGF upon treatment of HeLa cells with the compound, demonstrating its inhibitory effect at the cellular level. (c) 2012 Elsevier Ltd. All rights reserved.