Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha 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.
Osada
Mayuko
M
Department of Chemical Biology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 Japan.
Imaoka
Susumu
S
Funae
Yoshihiko
Y
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D047310:Apigenin / Q000378:metabolism*; D002460:Cell Line; D003035:Cobalt / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D003035:Cobalt; D047310:Apigenin