Abstract
Hypoxia-inducible factor-1 (HIF-1) has a central role in cellular responses to hypoxia, including the transcriptional activation of a number of genes involved in angiogenesis in tumors. We found that curcumin, a natural, biologically active compound isolated from the commonly used spice turmeric, significantly decreases hypoxia-induced HIF-1alpha protein levels in HepG2 hepatocellular carcinoma cells. Moreover, curcumin suppressed the transcriptional activity of HIF-1 under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major HIF-1 target angiogenic factor. Curcumin also blocked hypoxia-stimulated angiogenesis in vitro and down-regulated HIF-1alpha and VEGF expression in vascular endothelial cells. These findings suggest that curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1alpha-mediated angiogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Growth Processes / drug effects
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Cell Hypoxia / drug effects
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Cell Hypoxia / physiology
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Curcumin / pharmacology*
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Down-Regulation / drug effects
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Endothelial Cells / pathology
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Hepatoblastoma / blood supply*
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Hepatoblastoma / drug therapy
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Hepatoblastoma / genetics
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Hepatoblastoma / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Liver Neoplasms / blood supply*
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Liver Neoplasms / drug therapy
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Transcriptional Activation / drug effects
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Transfection
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Curcumin