title: Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells.
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.
  
  
  CONCLUSIONS
  Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.
authors.affiliation: Department of Neurosurgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Wan-Soo
authors.initials: WS
authors.lastname: Yoon
authors.affiliation: Clinical Research Laboratory, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Yeom
authors.affiliation: Clinical Research Laboratory, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Chung
authors.affiliation: Department of Neurosurgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Chung
authors.affiliation: Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sin-Soo
authors.initials: SS
authors.lastname: Jeun
keywords: Autophagy; Glioma; Memantine; N-methyl-D-aspartate