title: Naringin suppresses cell metastasis and the expression of matrix metalloproteinases (MMP-2 and MMP-9) via the inhibition of ERK-P38-JNK signaling pathway in human glioblastoma.
abstract: Naringin (4',5,7-trihydroxyflavanone 7-rhamnoglucoside), a natural flavonoid, has pharmacological properties. In the present study, we investigated the anti-metastatic activity of naringin and its molecular mechanism(s) of action in human glioblastoma cells. Naringin exhibits inhibitory effects on the invasion and adhesion of U87 cells in a concentration-dependent manner by Matrigel Transwell and cell adhesion assays. Naringin also inhibited the migration of U87 cells in a concentration-dependent manner by wound-healing assay. Additional experiments showed that naringin treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase (MMP)-2 and MMP-9 using a gelatin zymography assay and western blot analyses. Furthermore, naringin was able to reduce the protein phosphorylation of extracellular signal-regulated kinase ERK, p38 mitogen-activated protein kinase and c-Jun N-terminal kinase by western blotting. Collectively, our data showed that naringin attenuated the MAPK signaling pathways including ERK, JNK and p38 and resulted in the downregulation of the expression and enzymatic activities of MMP-2, MMP-9, contributing to the inhibition of metastasis in U87 cells. These findings proved that naringin may offer further application as an antimetastatic agent.
authors.affiliation: Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08, Faculty of Medicine, University of Monastir, BP5019, 5000 Monsatir, Tunisia. Electronic address: sonia_aroui2002@yahoo.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Aroui
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
authors.forename: Bakhta
authors.initials: B
authors.lastname: Aouey
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.affiliation: ERL CNRS/University of Poitiers n°7368, Georges Bonnet Street N°1, TSA 51106, 86073 Poitiers Cedex 9, France.
authors.forename: Annie-Claire
authors.initials: AC
authors.lastname: Meunier
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
authors.affiliation: Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08, Faculty of Medicine, University of Monastir, BP5019, 5000 Monsatir, Tunisia.
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Kenani
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000517:prevention & control*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D044950:Flavanones; D061965:Matrix Metalloproteinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C005274:naringin
keywords: Glioblastoma; Invasion; Matrix metalloproteinases; Naringin; Signaling pathways