title: Naringin inhibits the invasion and migration of human glioblastoma cell via downregulation of MMP-2 and MMP-9 expression and inactivation of p38 signaling pathway.
abstract: Gliomas are the most common and malignant primary brain tumors. They are associated with a poor prognosis despite the availability of multiple therapeutic options. Naringin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong anti-proliferative and anti-cancer properties. However, there are no reports describing its effects on the invasion and migration of glioblastoma cell lines. Our results showed that the treatment of U251 glioma cell lines with different concentrations of naringin inhibited the invasion and migration of these cells. In addition, we revealed a decrease in the levels of matrix metalloproteinases (MMP-2) and (MMP-9) expression as well as proteinase activity in U251 glioma cells. In contrast, the expression of tissue inhibitor of metalloproteinases (TIMP-1) and (TIMP-2) was increased. Furthermore, naringin treatment decreased significantly the phosphorylated level of p38. Combined treatment with a p38 inhibitor (SB203580) resulted in the synergistic reduction of MMP-2 and MMP-9 expressions correlated with an increase of TIMP-1 and TIMP-2 expressions and the anti-invasive properties. However, p38 chemical activator (anisomycin) could block these effects produced by naringin, suggesting a direct downregulation of the p38 signaling pathway. These data suggest that naringin may have therapeutic potential for controlling invasiveness of malignant gliomas by inhibiting of p38 signal transduction pathways.
authors.affiliation: Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08, Faculty of Medicine, University of Monastir, BP 5019, 5000, Monsatir, Tunisia. sonia_aroui2002@yahoo.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Aroui
authors.affiliation: ERL CNRS/University of Poitiers n°7368, Georges Bonnet Street N°1, TSA 51106, 86073, Poitiers Cedex 9, France.
authors.forename: Feten
authors.initials: F
authors.lastname: Najlaoui
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 Venins and Therapeutic Biomolecules, Institute Pasteur of Tunis, LR11IPT08, 13, 1002, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Laajimi
authors.affiliation: Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08, Faculty of Medicine, University of Monastir, BP 5019, 5000, Monsatir, Tunisia.
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Kenani
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
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D044950:Flavanones; D007093:Imidazoles; D011725:Pyridines; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C005274:naringin; C093642:SB 203580
keywords: Glioblastoma; Invasion; Matrix metalloproteinases; Migration; Naringin; Signaling pathways