Abstract
NF-kappaB acts as a signal transducer during tumor progression, cell invasion, and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis factor-alpha-induced nuclear entry of NF-kappaB/p65. However, only a few reports suggest that DMF inhibits tumor metastasis; also the molecular mechanisms underlying the inhibition of metastasis are poorly understood. We investigated the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line, B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the expression and activities of MMPs. DMF also inhibited the nuclear entry of NF-kappaB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results suggest that DMF is potentially useful as an anti-metastatic agent for the treatment of malignant melanoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / physiology
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Dimethyl Fumarate
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Fumarates / therapeutic use*
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Fumarates / toxicity
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Immunosuppressive Agents / pharmacology*
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Immunosuppressive Agents / toxicity
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Matrix Metalloproteinase Inhibitors*
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Melanoma / drug therapy*
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Melanoma / enzymology
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Melanoma / secondary
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / enzymology
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Melanoma, Experimental / secondary
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Mice
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Mice, Inbred C57BL
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Neoplasm Invasiveness
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / enzymology
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Skin Neoplasms / pathology
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Transcription Factor RelA / antagonists & inhibitors
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Transcription Factor RelA / metabolism
Substances
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Fumarates
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Immunosuppressive Agents
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Matrix Metalloproteinase Inhibitors
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NF-kappa B
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Transcription Factor RelA
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Extracellular Signal-Regulated MAP Kinases
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Dimethyl Fumarate