Title:AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells
Volume: 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
Affiliation:
- Memory Clinic of Fundacio ACE, Institut Catala de Neurciencies Aplicades, C/Marques de Sentmenat, 57-08029 Barcelona,Spain
Keywords:
AMPA glutamate receptor, antagonist, cancer, CFM-2, survivin, cells, ionotropic glutamate receptors.
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.
