Abstract
Hypoxia-inducible factor (HIF)-1α is a key regulator associated with tumorigenesis, angiogenesis, and metastasis. HIF-1α regulation under hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. Here, we demonstrate that diacetyl atractylodiol (DAA) from Atractylodes japonica (A. japonica) is a potent HIF-1α inhibitor that inhibits the Akt signaling pathway. DAA dose-dependently inhibited hypoxia-induced HIF-1α and downregulated Akt signaling without affecting the stability of HIF-1α protein. Furthermore, DAA prevented hypoxia-mediated angiogenesis based on in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays. Therefore, DAA might be useful for treatment of hypoxia-related tumorigenesis, including angiogenesis. [BMB Reports 2016; 49(9): 508-513].
MeSH terms
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Atractylodes / chemistry
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Atractylodes / metabolism
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Blotting, Western
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Chorioallantoic Membrane / drug effects
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Chorioallantoic Membrane / physiology
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Cobalt / toxicity
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Down-Regulation / drug effects
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Enediynes / pharmacology*
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HeLa Cells
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Human Umbilical Vein Endothelial Cells
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Humans
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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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Neovascularization, Physiologic / drug effects*
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism*
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Real-Time Polymerase Chain Reaction
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Signal Transduction / drug effects*
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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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Enediynes
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Hypoxia-Inducible Factor 1, alpha Subunit
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Vascular Endothelial Growth Factor A
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Cobalt
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diacetylatractylodiol
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Proto-Oncogene Proteins c-akt
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cobaltous chloride