J Korean Neurosurg Soc.  2017 Feb;60(2):130-137. 10.3340/jkns.2016.0101.006.

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

Affiliations
  • 1Department of Neurosurgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
  • 2Clinical Research Laboratory, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
  • 3Institute of Catholic Integrative Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Korea.
  • 4Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. ssjeun@catholic.ac.kr

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.

Keyword

Memantine; Autophagy; N-methyl-D-aspartate; Glioma

MeSH Terms

Autophagy*
Cell Death
Cell Line
Gastrin-Secreting Cells
Glioma*
Memantine*
N-Methylaspartate
RNA, Small Interfering
Transfection
Vacuoles
Memantine
N-Methylaspartate
RNA, Small Interfering
Full Text Links
  • JKNS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error