Targeting cancer cell metabolism with metformin, dichloroacetate and memantine in glioblastoma (gbm)

AIM:To investigate the effects of metformin, dichloroacetate (DCA), and memantine on T98G and U87-MG human glioblastoma (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.Fifteen 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.Fifteen 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.