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Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF‐1α protein
Author(s) -
Osada Mayuko,
Imaoka Susumu,
Funae Yoshihiko
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.036
Subject(s) - apigenin , angiogenesis , vascular endothelial growth factor , hypoxia inducible factors , hif1a , chemistry , hypoxia (environmental) , heat shock protein , vascular endothelial growth factor a , microbiology and biotechnology , hsp90 , cancer research , biology , biochemistry , vegf receptors , flavonoid , gene , organic chemistry , oxygen , antioxidant
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) α. We investigated the effect of apigenin on the interaction of HIF‐1α with heat shock protein 90 (Hsp90), which is reported to be important for the stabilization of HIF‐1α, and found that VEGF expression was inhibited via degradation of HIF‐1α through interference with the function of Hsp90.