Glutamate antagonists limit tumor growth.
Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-d-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca(2+) dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.
Rzeski
W
W
Department of Pediatric Neurology, Children's Hospital, Charite-Virchow Campus, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany.
Turski
L
L
Ikonomidou
C
C
D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009369:Neoplasms / Q000503:physiopathology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013852:Thiotepa / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000970:Antineoplastic Agents; D018691:Excitatory Amino Acid Antagonists; D006131:Growth Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; D001569:Benzodiazepines; D018698:Glutamic Acid; D014747:Vinblastine; D016291:Dizocilpine Maleate; D003520:Cyclophosphamide; D013852:Thiotepa; D002945:Cisplatin