Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF

Nicola J. Mabjeesh, Margaret T. Willard, Wayne B. Harris, He Ying Sun, Ruoxiang Wang, Hua Zhong, Jay N. Umbreit, Jonathan W. Simons

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1α and HIF-1β subunits. While HIF-1β is constitutively expressed, HIF-1α is targeted to proteasome degradation under normoxic conditions. Under hypoxia, HIF-1α is stabilized and heterodimerizes with HIF-1β. Iron chelators have also been reported to stabilize HIF-1α protein and activate HIF-1. In this study, we investigated the effects of dibenzoylmethane (DBM), a natural dietary compound and an iron chelator, on HIF-1 pathway. We found that DBM increases HIF-1α protein levels in a dose- and time-dependent manner. This induction was accompanied with activation of HIF-1, measured by reporter gene assay and increased production of its downstream target, the vascular endothelial growth factor. Mechanistically, HIF-1α was stabilized by DBM at a step prior to ubiquitination. The effect of DBM on HIF-1 and its low toxicity profile might be therapeutically beneficial in ischemic diseases.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume303
Issue number1
DOIs
StatePublished - 28 Mar 2003
Externally publishedYes

Keywords

  • Cardiomyocyte
  • Dibenzoylmethane
  • HIF-1α
  • Prostate cancer cells
  • VEGF

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