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

Metallomics. 2017 Aug 16;9(8):1176-1184. doi: 10.1039/c7mt00049a.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Coordination Complexes / pharmacology*
  • Female
  • Fibrosarcoma / drug therapy*
  • Fibrosarcoma / enzymology
  • Fibrosarcoma / pathology
  • Gallium / chemistry
  • Gallium / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • chloro(N-(5-chloro-2-hydroxyphenyl)aspartato)gallium(III)
  • Gallium
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP14 protein, human
  • Matrix Metalloproteinase 14