Targeting Cancer Cell Metabolism with Metformin, Dichloroacetate and Memantine in Glioblastoma (GBM)

Turk Neurosurg. 2021;31(2):233-237. doi: 10.5137/1019-5149.JTN.29176-20.3.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dichloroacetic Acid / pharmacology*
  • Dichloroacetic Acid / therapeutic use
  • Dopamine Agents / pharmacology
  • Dopamine Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Memantine / pharmacology*
  • Memantine / therapeutic use
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • Dopamine Agents
  • Hypoglycemic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Metformin
  • Dichloroacetic Acid
  • Memantine