Abstract
Angiogenesis is important in the development and progression of cancer, therefore the therapeutic approach based on anti-angiogenesis may represent a promising therapeutic option. KR-31831 is a novel anti-ischemic agent. Previously, we reported the anti-angiogenic activity of KR-31831. In the present study we investigated the molecular mechanisms underlying anti-angiogenic activity of KR-31831. We show that KR-31831 inhibits vascular endothelial growth factor (VEGF)-induced proliferation and tube formation via release of intracellular Ca2+ and phosphorylation of extra-cellular regulated kinase 1/2 (Erk 1/2) in human umbilical vein endothelial cells (HUVECs). Moreover, the expression of VEGF receptor 2 (VEGFR2, known as Flk-1 or KDR) was reduced by the treatment of KR-31831. These results suggest that KR-31831 may have inhibitory effects on tumor angiogenesis through down-regulation of KDR expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzopyrans / pharmacology*
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Cell Cycle / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Collagen / metabolism
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Drug Combinations
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Endothelium, Vascular / drug effects*
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Humans
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Imidazoles / pharmacology*
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Immunoblotting
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Laminin / metabolism
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neovascularization, Pathologic / prevention & control*
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Phosphorylation
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Proteoglycans / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Umbilical Veins / cytology
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Vascular Endothelial Growth Factor A / antagonists & inhibitors*
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Vascular Endothelial Growth Factor A / pharmacology
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism*
Substances
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Benzopyrans
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Drug Combinations
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Imidazoles
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KR 31831
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Laminin
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Proteoglycans
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RNA, Messenger
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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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Collagen
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Vascular Endothelial Growth Factor Receptor-2
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3