Abstract
Metastasis is the main cause of cancer mortality. In this study, we investigated the effects of surfactin, a cyclic lipopeptide produced by Bacillus subtilis, on cancer metastasis in vitro and the underlying molecular mechanisms involved. Surfactin inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion, migration and colony formation of human breast carcinoma cells. Western blot analysis, gelatin zymography and reverse transcription-PCR analysis revealed that matrix metalloproteinase-9 (MMP-9) expression and activation was significantly suppressed by surfactin in a dose-dependent manner. Surfactin attenuated TPA-induced nuclear translocation and activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Furthermore, surfactin strongly repressed the TPA-induced phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Treatment with specific inhibitors of Akt and ERK suppressed MMP-9 expression and activation. These results suggest that the surfactin-mediated inhibition of breast cancer cell invasion and MMP-9 expression involves the suppression of the NF-κB, AP-1, phosphatidylinositol 3-kinase (PI-3K)/Akt and the ERK signaling pathways. Thus surfactin may have potential value in therapeutic strategies for the treatment of breast cancer metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibiotics, Antineoplastic / pharmacology*
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Apoptosis / drug effects
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Blotting, Western
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Breast Neoplasms / chemically induced
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Breast Neoplasms / pathology
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Breast Neoplasms / prevention & control*
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Carcinogens / pharmacology*
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Cell Movement / drug effects*
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Cell Proliferation / drug effects
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Lipopeptides / pharmacology*
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Matrix Metalloproteinase 9 / chemistry*
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Neoplasm Invasiveness
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Peptides, Cyclic / pharmacology*
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Tetradecanoylphorbol Acetate / adverse effects*
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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Tumor Cells, Cultured
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Wound Healing / drug effects
Substances
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Antibiotics, Antineoplastic
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Carcinogens
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Lipopeptides
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NF-kappa B
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Peptides, Cyclic
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RNA, Messenger
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Transcription Factor AP-1
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surfactin peptide
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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MMP9 protein, human
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Matrix Metalloproteinase 9
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Tetradecanoylphorbol Acetate