Journal
FEBS LETTERS
Volume 575, Issue 1-3, Pages 59-63Publisher
WILEY
DOI: 10.1016/j.febslet.2004.08.036
Keywords
apigenin; angiogenesis; vascular endothelial growth factor; hypoxia; hypoxia-inducible factor; heat shock protein 90
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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. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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