Abstract
The chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. Our previous studies showed that Nordy, a synthetic chiral compound of nordihydroguaiaretic acid, inhibited the growth and angiogenesis of various malignant tumors. In this study we examined the capacity of Nordy to regulate CXCR4-mediated production of angiogenic factors by human glioblastoma cells. We found that Nordy potently inhibited CXCR4 ligand SDF-1-induced production of IL-8 and vascular endothelial cell growth factor, two important angiogenic factors implicated in the progression of malignant tumors. Further study revealed that the effect of Nordy was attributable to its down-regulation of the expression of functional CXCR4 in glioblastoma cells. These results suggest that the anti-cancer activity of Nordy is due, at least in part, to its suppression of the chemokine receptor CXCR4 thus reducing the production of angiogenic factors by tumor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Angiogenic Proteins / metabolism
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Animals
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Antineoplastic Agents / pharmacology*
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Brain Neoplasms / drug therapy
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Brain Neoplasms / metabolism*
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Cell Line, Tumor
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Down-Regulation
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Gene Expression Regulation, Neoplastic / drug effects*
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Glioma / drug therapy
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Glioma / metabolism*
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Humans
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Lignans / pharmacology*
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Lipoxygenase Inhibitors / pharmacology
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Masoprocol / chemistry
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Masoprocol / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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RNA, Messenger / analysis
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Receptors, CXCR4 / drug effects*
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Receptors, CXCR4 / metabolism
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Vascular Endothelial Growth Factor A / 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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Angiogenic Proteins
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Antineoplastic Agents
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Interleukin-8
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Lignans
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Lipoxygenase Inhibitors
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RNA, Messenger
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Receptors, CXCR4
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Vascular Endothelial Growth Factor A
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nordy
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Masoprocol