Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells

J Korean Neurosurg Soc. 2017 Mar;60(2):130-137. doi: 10.3340/jkns.2016.0101.006. Epub 2017 Mar 1.

Abstract

Objective: Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines.

Methods: Glioma cell lines (T-98 G and U-251 MG) were used for this study.

Results: The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells.

Conclusion: Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.

Keywords: Autophagy; Glioma; Memantine; N-methyl-D-aspartate.