Abstract
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Chromones / pharmacology*
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Collagen / metabolism
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Drug Combinations
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Enzyme Activation / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Laminin / metabolism
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MAP Kinase Signaling System / drug effects
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Matrix Metalloproteinase Inhibitors
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NF-kappa B / antagonists & inhibitors*
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Neoplasm Invasiveness
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Neoplasms / enzymology*
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Neoplasms / genetics
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Neoplasms / pathology*
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Proteoglycans / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factor AP-1 / genetics
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Transcriptional Activation / drug effects
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Chromones
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Drug Combinations
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Laminin
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Matrix Metalloproteinase Inhibitors
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NF-kappa B
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Proteoglycans
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Transcription Factor AP-1
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matrigel
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capillarisin
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Collagen
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Matrix Metalloproteinase 9
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Tetradecanoylphorbol Acetate