1. Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells
- Author
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Mi-Young Yeom, Eun-Sun Kang, Sin-Soo Jeun, Yong-An Chung, Wan-Soo Yoon, and Dong-Sup Chung
- Subjects
0301 basic medicine ,Small interfering RNA ,Programmed cell death ,Vacuole ,03 medical and health sciences ,0302 clinical medicine ,Memantine ,Glioma ,Autophagy ,medicine ,business.industry ,General Neuroscience ,Transfection ,medicine.disease ,030104 developmental biology ,N-methyl-D-aspartate ,Cancer cell ,Laboratory Investigation ,Cancer research ,Surgery ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - 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.
- Published
- 2017