Neurodegeneration, Neuroprotection and Disease-Oriented NeuroscienceResearch PaperInhibition of metalloproteinases derived from tumours: new insights in the treatment of human glioblastoma
Section snippets
Commercial suppliers
Temozolomide and gelatin (type A) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Cell culture media and growth supplements were obtained from Cambrex Bio Science, Walkersville, Inc. (Walkersville, MD, USA). Bio-Rad Protein Assays were purchased from Bio-Rad (Hercules, CA, USA). Trypan Blue was from Sigma/RBI (Natick, MA, USA). Cell Titer 96 Aqueous One Solution Cell Proliferation assays were obtained from Promega (Milan, Italy). RayBio® Human MMP-2 ELISA kit was from RayBiotech Inc
Results
The N-isopropoxy-biphenylsulfonamide hydroxamic acids 1 and 2 (Fig. 1) were employed in cell treatment experiments.
In test tube assays, nanomolar concentrations of compounds 1 and 2 resulted to selectively inhibit the activity of the human recombinant matrix metalloproteinases, MMP-2, MMP-9 and MMP-12 (Table 1).
The ability of the compounds to affect MMP-2 activity at such concentrations (12 nM compound 1, 1 nM compound 2 and 25 nM CGS_27023A) prompted us to investigate their ability to affect
Discussion
Gliomas are the most prevalent primary brain tumours. Between gliomas, GBM (World Health Organization Grade IV astrocytoma) is the most common and aggressive primary brain tumor in adults, and the median survival of 12 months for patients has not changed during the last few years (Desjardins et al., 2005). Therefore, new approaches are essential for the treatment of these patients, especially because the occurrence of gliomas is increasing (Hess et al., 2004, Johannesen et al., 2004). Invasive
Conclusion
In conclusion, taken together, these data suggest that this combination of drugs may have good therapeutic potential for the treatment of brain tumours. The ability of glioma cells to proliferate quickly and to infiltrate the surrounding brain tissues, escaping current therapeutic modalities, could be minimized using the combined treatment. These co-treatments could block the growth of the tumour by means of an alkylating agent, such as TMZ, and could stop the invasiveness through MMP-2
Acknowledgments
This study was supported by the Italian Ministry of University and Scientific Research (PRIN 2007). The authors thank Dr. Marina Fabbi from National Institute for Cancer Research of Genoa for providing the human U87MG cell line.
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These authors contributed equally for this manuscript.