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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2007

AutorInnen: Stepulak, A; Sifringer, M; Rzeski, W; Brocke, K; Gratopp, A; Pohl, EE; Turski, L; Ikonomidou, C

Titel: AMPA antagonists inhibit the extracellular signal regulated kinase pathway and suppress lung cancer growth.

Quelle: Cancer Biol Ther. 2007; 6(12):1908-1915

Autor/innen der Vetmeduni Vienna:

Pohl Elena

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!

Antagonists at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors limit growth of human cancers in vitro. However, the mechanism of anticancer action of AMPA antagonists is not known. Here we report that the AMPA antagonists GYKI 52466 and CFM-2 inhibit the extracellular signal regulated kinase (ERK1/2) pathway, an intracellular signaling cascade which is activated by growth factors and controls proliferation of lung adenocarcinoma cells. AMPA antagonists reduced phosphorylation of cAMP-responsive element binding protein (CREB), suppressed expression of cyclin D1, upregulated the cell cycle regulators and tumor suppressor proteins p21 and p53 and decreased number of lung adenocarcinoma cells in G2 and S phases of the cell cycle. These findings reveal potential mechanism of antiproliferative action of AMPA antagonists and indicate that this class of compounds may be useful in the therapy of human cancers.

Keywords Pubmed: Adenocarcinoma/enzymology
Antineoplastic Agents/pharmacology
Cell Cycle/drug effects
Cell Line, Tumor/drug effects
Cell Line, Tumor/metabolism
Drug Screening Assays, Antitumor
Enzyme Activation/drug effects
Excitatory Amino Acid Antagonists/pharmacology*
Gene Expression Regulation, Neoplastic/drug effects
Lung Neoplasms/enzymology
Lung Neoplasms/pathology*
Mitogen-Activated Protein Kinase 1/antagonists & inhibitors*
Mitogen-Activated Protein Kinase 3/antagonists & inhibitors*
Neoplasm Proteins/biosynthesis
Neoplasm Proteins/genetics
Phosphorylation/drug effects
Protein Processing, Post-Translational/drug effects
Receptors, AMPA/antagonists & inhibitors*
Signal Transduction/drug effects*
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/antagonists & inhibitors*

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