A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity.
Fiche publication
Date publication
août 2017
Journal
Metallomics : integrated biometal science
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ETIQUE Nicolas, Pr MORJANI Hamid, Dr BRASSART Bertrand
Tous les auteurs :
Mohsen A, Collery P, Garnotel R, Brassart B, Etique N, Mohamed Sabry G, Elsherif Hassan R, Jeannesson P, Desmaële D, Morjani H
Lien Pubmed
Résumé
In this study, we investigated the effect of [N-(5-chloro-2-hydroxyphenyl)-l-aspartato] chlorogallate (GS2), a new water soluble gallium complex, on cell invasion and on the expression and activity of matrix metalloproteinases (MMPs) in human metastatic HT-1080 fibrosarcoma and MDA-MB 231 breast carcinoma cells. The effect on cell invasion was studied using a modified Boyden chamber coated with a type-I collagen. We analyzed the effect of GS2 on MMP-2, MMP-9, and MMP-14 via zymography and enzymatic assay using high affinity fluorogenic substrates. The expression of MMP mRNA was analyzed via qRT-PCR. GS2 induced a decrease in cell invasion. A dose-dependent inhibition effect was observed on the activities of MMP-2, MMP-9, and MMP-14 with the IC50 values of 168, 82, and 20 μM, respectively. A decrease in the expression of MMP-14 mRNA was observed in both cell lines, whereas the expression of MMP-2 and MMP-9 mRNA was decreased only in the MDA-MB231 cells. Data obtained for the expression of MMP-14 mRNA were confirmed via Western blotting. In fact, MMP-14 expression was decreased in the presence of GS2. Overall, these data show that GS2 is a promising compound for anti-invasive and anticancer therapy.
Mots clés
Antineoplastic Agents, pharmacology, Breast Neoplasms, drug therapy, Cell Movement, drug effects, Cell Proliferation, drug effects, Coordination Complexes, pharmacology, Female, Fibrosarcoma, drug therapy, Gallium, chemistry, Gene Expression Regulation, Enzymologic, drug effects, Humans, Matrix Metalloproteinase 14, genetics, Matrix Metalloproteinase 2, genetics, Matrix Metalloproteinase 9, genetics, Neoplasm Invasiveness, Tumor Cells, Cultured
Référence
Metallomics. 2017 Aug;: