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

Author(s): Domingo Sanchez Ruiz*, Hella Luksch, Marco Sifringer, Achim Temme, Christian Staufner, Wojciech Rzeski, Jenny Marzahn, Aneta Grabarska, Chrysanthy Ikonomidou, Andrzej Stepulak.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 18 , Issue 4 , 2018

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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.

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Article Details

VOLUME: 18
ISSUE: 4
Year: 2018
Page: [591 - 596]
Pages: 6
DOI: 10.2174/1871520618666180228123406
Price: $58

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