title: Acteoside inhibits PMA-induced matrix metalloproteinase-9 expression via CaMK/ERK- and JNK/NF-κB-dependent signaling.
abstract: METHODS
  Acteoside, an active phenylethanoid glycoside found in bitter tea and many medicinal plants, displays chemopreventive properties. The aim of our study was to determine the effect of acteoside on tumor invasion and migration; the possible mechanisms involved in this inhibition were investigated in human fibrosarcoma HT-1080 cells.
  
  
  RESULTS
  We employed invasion, migration and gelatin zymography assays to characterize the effect of acteoside on HT-1080 cells. Transient transfection assays were performed to investigate gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action. We found that acteoside suppresses phorbol-12-myristate-13-acetate (PMA)-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-κB activation. In addition, acteoside repressed the PMA-induced phosphorylation of ERK1/2 (ERK, extracellular regulated kinase) and JNK1/2. Further, we found that acteoside decreased the PMA-induced influx of Ca(2+) and repressed PMA-induced calmodulin-dependent protein kinase (CaMK) phosphorylation. Furthermore, treatment with BAPTA/AM, W7, or capsazepine markedly decreased PMA-induced MMP-9 secretion and cell migration, as well as ERK and JNK/NF-κB activation.
  
  
  CONCLUSIONS
  Acteoside inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+) -dependent CaMK/ERK and JNK/NF-κB-signaling pathways. Acteoside therefore has the potential to be a potent anticancer agent in therapeutic strategies for fibrosarcoma metastasis.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Park
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism; D059808:Polyphenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D005960:Glucosides; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D048055:Mitogen-Activated Protein Kinase 8; D016328:NF-kappa B; D010636:Phenols; D013755:Tetradecanoylphorbol Acetate; C058956:acteoside; D059808:Polyphenols; C016658:phorbolol myristate acetate