title: Resveratrol induces MMP-9 and cell migration via the p38 kinase and             PI-3K pathways in HT1080 human fibrosarcoma cells.
abstract: Trans-3,4',5-trihydroxystilbene (resveratrol) is a grape polyphenol present             in various plants, food products, red wine and grapes. Resveratrol has anti-inflammatory,             anticarcinogenic, anti-oxidant and anti-aging properties. Matrix metalloproteinases             (MMPs) are key enzymes involved in the degradation of the extracellular matrix,             and their expression may be regulated in cancer metastasis. In the present study,             we aimed to evaluate the effect of resveratrol on MMPs and cell migration, and             to understand the mechanism of action in HT1080 human fibrosarcoma cells. We found             that resveratrol inhibited HT1080 cell viability at various concentrations as             detected by the MTT assay and FACS analysis. However, resveratrol dramatically             increased the activation and expression of MMP-9 in a dose- and time-dependent             manner, as determined by gelatin zymography assay and western blot analysis. We             also discovered that resveratrol enhanced the migratory ability of HT1080 cells,             as determined by the wound healing assay, and decreased the phosphorylation of             p38 kinase. Moreover, the Akt kinase was inhibited by resveratrol in the HT1080             cells. The inhibition of p38 and Akt kinases with SB203580 and LY294002 further             increased resveratrol-induced MMP-9 as well as cell migration in the HT1080 cells.             Our results suggest that resveratrol regulates MMP-9 and migratory abilities through             the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences,                     Kongju National University, Gongju, Chungnam 314-701, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Gweon
authors.forename: Song Ja
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol