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Published online on May 1, 2001, 10.1073/pnas.091113598
PNAS | May 22, 2001 | vol. 98 | no. 11 | 6372-6377


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From the Cover
Medical Sciences
 Glutamate antagonists limit tumor growth

Wojciech Rzeski*,dagger , Lechoslaw TurskiDagger , and Chrysanthy Ikonomidou*,§

* Department of Pediatric Neurology, Children's Hospital, Charite-Virchow Campus, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany; and Dagger  Solvay Pharmaceuticals Research Laboratories, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands

Communicated by Martin Lindauer, University of Würzburg, Würzburg, Germany, March 7, 2001 (received for review September 13, 2000)

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 Ca2+ 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.

dagger Present address: Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, PL-20033 Lublin, Poland.

§ To whom reprint requests should be addressed. E-mail: hrissanthi.ikonomidou{at}charite.de.

www.pnas.org/cgi/doi/10.1073/pnas.091113598
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Related Commentary in PNAS:

Glutamate antagonists: Deadly liaisons with cancer
Esper A. Cavalheiro and John W. Olney
PNAS 2001 98: 5947-5948. [Extract] [Full Text]  



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