title: Surfactin suppresses TPA-induced breast cancer cell invasion through the inhibition of MMP-9 expression.
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.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Ji
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Younghee
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002273:Carcinogens / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010456:Peptides, Cyclic / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D055666:Lipopeptides; D016328:NF-kappa B; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C009365:surfactin peptide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate