Turkish Neurosurgery
Targeting Cancer Cell Metabolism with Metformin, Dichloroacetate and Memantine in Glioblastoma (GBM)
Gulsah Albayrak1, Ece Konac1, Umit Akın Dere2, Hakan Emmez2
1GAZI UNIVERSITY, Department of Medical Biology and Genetics, Ankara,
2GAZI UNIVERSITY, Department of Neurosurgery, Ankara,
DOI: 10.5137/1019-5149.JTN.29176-20.3

Aim:Glioblastoma (GBM) is the most common form of central nervous system tumor. Advances in targeted therapy and immunotherapy are yet to be effective in improving the overall survival rate for GBM patients. Thus, there is an ongoing demand for alternative treatments. In this study, we investigated the effects of metformin, dichloroacetate (DCA), and memantine on T98G and U87-MG human GBM cells to target tumor cell metabolism in a multi-directional manner. Material and Methods:IC50 levels for metformin, DCA, metformin+DCA and memantine were determined by MTT assay in T98G and U87-MG cells in vitro. Casp3, Bcl-2, Bax, c-Myc and GSK-3B protein expressions were investigated post treatments. 15 GBM+ tumor tissues were assessed for Casp-3, Bcl-2, Bad, Bax for apoptotic protein expression patterns.Results:Cancer cell metabolism targeting drugs metformin, DCA, metformin+DCA and memantine induced cytotoxicity in a dose-dependent manner in T98G and U87-MG cells. IC50 for memantine is found as 0.5 mM (p<0.01) which is nearly 10 times lower concentration than that of metformin. 15 GBM+ tumor tissues had differential apoptotic protein expressions.Conclusion:Memantine exerted anti-cancer mechanism of action in T98G and U87-MG cells, however, such a mechanism requires deeper investigation for GBM treatment.

Corresponding author : Gulsah Albayrak