Abstract
Apigenin is a non-toxic dietary flavonoid with anti-tumor properties. We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition. However, the effect of apigenin in angiogenesis remains to be elucidated. Angiogenesis is the formation of new blood vessels and is required for tumor growth and metastasis. In this study, we showed that apigenin-inhibited expression of HIF-1 and VEGF in different cancer cells under both normoxic and hypoxic conditions. We demonstrated that apigenin significantly inhibited tumor angiogenesis in vivo, by using both the chicken chorioallantoic membrane and Matrigel plug assays. The inhibition of tumor angiogenesis was associated with the decrease of HIF-1 and VEGF in tumor tissues. Taken together, our results show that apigenin suppresses tumor angiogenesis through HIF-1 and VEGF expression.
MeSH terms
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Animals
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Apigenin / pharmacology*
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Apoptosis / drug effects
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Binding Sites
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Cell Division / drug effects
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Cell Line, Tumor
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Chick Embryo
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Chorioallantoic Membrane / drug effects
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Chorioallantoic Membrane / metabolism
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Collagen / metabolism
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Drug Combinations
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Female
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Flow Cytometry
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Hypoxia
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Laminin / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasms, Experimental / blood supply*
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Neoplasms, Experimental / metabolism
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Neovascularization, Pathologic / prevention & control*
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Promoter Regions, Genetic
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Proteoglycans / metabolism
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Signal Transduction
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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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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Drug Combinations
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HIF1A protein, human
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1, alpha Subunit
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Laminin
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Proteoglycans
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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matrigel
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Apigenin
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Collagen