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AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells

[ Vol. 18 , Issue. 4 ]

Author(s):

Domingo Sanchez Ruiz*, Hella Luksch, Marco Sifringer, Achim Temme, Christian Staufner, Wojciech Rzeski, Jenny Marzahn, Aneta Grabarska, Chrysanthy Ikonomidou and Andrzej Stepulak   Pages 591 - 596 ( 6 )

Abstract:


Background: Glutamate receptors are widely expressed in different types of cancer cells. α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are ionotropic glutamate receptors which are coupled to intracellular signaling pathways that influence cancer cell survival, proliferation, and migration. Blockade of AMPA receptors by pharmacologic compounds may potentially constitute an effective tool in anticancer treatment strategies.

Method: Here we investigated the impact of the AMPA receptor antagonist CFM-2 on the expression of the protein survivin, which is known to promote cancer cell survival and proliferation. We show that CFM-2 inhibits survivin expression at mRNA and protein levels and decreases the viability of cancer cells. Using a stably transfected cell line which overexpresses survivin, we demonstrate that over-expression of survivin enhances cancer cell viability and attenuates CFM-2–mediated inhibition of cancer cell growth.

Result: These findings point towards suppression of survivin expression as a new mechanism contributing to anticancer effects of AMPA antagonists.

Keywords:

AMPA glutamate receptor, antagonist, cancer, CFM-2, survivin, cells, ionotropic glutamate receptors.

Affiliation:

Memory Clinic of Fundacio ACE, Institut Catala de Neurciencies Aplicades, C/Marques de Sentmenat, 57-08029 Barcelona, Department of Pediatric Neurology, Children´s Hospital, Carl Gustav Carus Medical Faculty, Technical University Dresden, 01307 Dresden, Department of Anesthesiology and Intensive Care, Charite-Universitaetsmedizin Berlin, 13353 Berlin, Department of Neurosurgery, Section Experimental Neurosurgery and Tumor Immunology, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Department of Paediatrics I, University Children`s Hospital, University of Heidelberg, 69120 Heidelberg, Department of Virology and Immunology, Maria Curie-Sklodowska University, 20-033 Lublin, Department of Pediatric Neurology, Children´s Hospital, Carl Gustav Carus Medical Faculty, Technical University Dresden, 01307 Dresden, Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Department of Neurology, University of Wisconsin, 53705 Madison, Wisconsin, Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin

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