Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF‐1α protein

Apigenin, a plant-derived flavone, is a potent inhibitor of cell proliferation and angiogenesis, but the mechanisms leading to the pathological anti-angiogenic effects of apigenin are still unclear. In this study, we found that apigenin inhibited the hypoxia-induced expression of vascular endothelial growth factor (VEGF) mRNA in human umbilical artery endothelial cells. Apigenin also suppressed the expression of erythropoietin mRNA, which is a typical hypoxia-inducible gene, via the degradation of hypoxia-inducible factor 1 (HIF-1) alpha. We investigated the effect of apigenin on the interaction of HIF-1alpha with heat shock protein 90 (Hsp90), which is reported to be important for the stabilization of HIF-1alpha, and found that VEGF expression was inhibited via degradation of HIF-1alpha through interference with the function of Hsp90.