Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / metabolism*
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Animals
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Antineoplastic Agents / metabolism
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Apigenin / metabolism*
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Cell Line
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Cobalt / metabolism
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Endothelial Cells / metabolism*
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism
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Erythropoietin / genetics
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Erythropoietin / metabolism
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Gene Expression Regulation
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HSP90 Heat-Shock Proteins / metabolism
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Humans
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Hypoxia
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Hypoxia-Inducible Factor 1, alpha Subunit
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Transcription Factors / metabolism*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism*
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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HIF1A protein, human
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HSP90 Heat-Shock Proteins
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Hypoxia-Inducible Factor 1, alpha Subunit
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Transcription Factors
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Vascular Endothelial Growth Factor A
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Erythropoietin
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Cobalt
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Apigenin