Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/27122
Título: The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells
Autor: Ribeiro, Mariana P. C. 
Nunes-Correia, Isabel 
Santos, Armanda E. 
Custódio, José B. A. 
Palavras-chave: Glutamate receptor antagonists; Antiestrogens; Melanoma; Cell proliferation
Data: 15-Fev-2014
Editora: Elsevier
Citação: RIBEIRO, Mariana P. C. [et al.] - The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells. "Experimental Cell Research". ISSN 0014-4827. Vol. 321 Nº. 2 (2014) p. 288-296
Título da revista, periódico, livro ou evento: Experimental Cell Research
Volume: 321
Número: 2
Resumo: Recent reports suggest that N-methyl-d-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination.
URI: https://hdl.handle.net/10316/27122
ISSN: 0014-4827
DOI: 10.1016/j.yexcr.2013.11.002
Direitos: openAccess
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