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.

Sonia Aroui 1, * Feten Najlaoui 2 Yassine Chtourou 3 Annie-Claire Meunier 2 Amel Laajimi 4 Abderraouf Kenani 1 Hamadi Fetoui 5
* Corresponding author
1 Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08. Faculty of Medicine
2 Université de Poitiers
3 UR11ES70 - Laboratory of Toxicology-Microbiology and Environmental Health
4 Laboratoire des Venins et Toxines, Institut Pasteur de Tunis
5 Animal Physiology Laboratory, Life Sciences Department
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.
Keywords : Signaling pathways Naringin Migration Matrix metalloproteinases Invasion Glioblastoma
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Journal articles
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Submitted on : Wednesday, December 21, 2016 - 3:07:09 PM
Last modification on : Thursday, March 7, 2019 - 11:46:54 AM

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Sonia Aroui, Feten Najlaoui, Yassine Chtourou, Annie-Claire Meunier, Amel Laajimi, et al.. 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.. Tumor Biology, Springer Verlag, 2016, 37 (3), pp.3831-9. ⟨10.1007/s13277-015-4230-4⟩. ⟨pasteur-01374978⟩

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