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

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.