A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity

作者：Mohsen Ahmed; Collery Philippe; Garnotel Roselyne; Brassart Bertrand; Etique Nicolas; Sabry Gilane Mohamed; Hassan Rasha Elsherif; Jeannesson Pierre; Desmaele Didier; Morjani Hamid

来源：Metallomics, 2017, 9(8): 1176-1184.

DOI：10.1039/c7mt00049a

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 mu M, 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.

• 出版日期2017-8-1