Abstract
Our previous study has demonstrated that the methanol extract of Hyul-Tong-Ryung (HM) specifically suppresses the phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) production through the inhibition of MMP-9 mRNA expression in MCF-7 human breast carcinoma cells. However, the molecular mechanisms involved in transcriptional suppression of MMP-9 by HM in PMA-induced MCF-7 cells are not known. In this study, we aimed to elucidate the molecular mechanisms involved in the inhibition of MMP-9 expression by HM in PMA-induced MCF-7 cells. The results of promoter assay and EMSA showed that HM specifically inhibits MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1). In addition, PMA-stimulated phosphorylation of extracellular signal regulated kinase 1/2 (ERK 1/2) was suppressed by HM treatment, whereas the phosphorylation of either c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) was not affected. HM could inhibit the PMA-induced MMP-9 expression through suppression of the transcriptional activity of MMP-9 gene in MCF-7 cells. These results indicate that HM inhibits PMA-induced MMP-9 expression by blocking the activation of activator protein-1 (AP-1) via extracellular signal regulated kinase 1/2 (ERK 1/2) signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / pathology
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Cell Line, Tumor
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DNA / genetics
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DNA / metabolism
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Drugs, Chinese Herbal / pharmacology*
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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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Gene Expression / drug effects*
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Gene Expression / genetics
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Genes, Reporter / genetics
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Mutation / genetics
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NF-kappa B / metabolism
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Phosphorylation / drug effects
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Promoter Regions, Genetic / genetics
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Protein Binding / genetics
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Protein Kinase Inhibitors / pharmacology
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Response Elements / genetics
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Tetradecanoylphorbol Acetate / pharmacology*
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Transcription Factor AP-1 / metabolism*
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Transcription Factor RelA / metabolism
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Transfection
Substances
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Drugs, Chinese Herbal
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Hyul-Tong-Ryung
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NF-kappa B
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Protein Kinase Inhibitors
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Transcription Factor AP-1
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Transcription Factor RelA
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DNA
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Matrix Metalloproteinase 9
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Tetradecanoylphorbol Acetate