Turkish Neurosurgery 2021 , Vol 31 , Num 2
Targeting Cancer Cell Metabolism with Metformin, Dichloroacetate and Memantine in Glioblastoma (GBM)
Gulsah ALBAYRAK1,Ece KONAC1,Umit Akin DERE2,Hakan EMMEZ2
1Gazi University, Faculty of Medicine, Department of Medical Biology and Genetics, Ankara, Turkey
2Gazi University, Faculty of Medicine, Department of Neurosurgery, Ankara, Turkey
DOI : 10.5137/1019-5149.JTN.29176-20.3 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. Keywords : Glioblastoma, Cancer cell, Metabolism, Metformin, Dichloroacetate, Memantine

Corresponding author : Ece KONAC, ecemercanoglu@yahoo.com