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Abstract:

Antidepressants have a controversial role with regard to their influence on cancer and immunity. Recently, we showed that fluoxetine administration induces an enhancement of the T-cell mediated immunity in naïve mice, resulting in the inhibition of tumor growth. Here we studied the effects of fluoxetine on lymphoma proliferation/apoptosis and immunity in tumor bearing-mice. We found an increase of apoptotic cells (active Caspase-3+) and a decrease of proliferative cells (PCNA+) in tumors growing in fluoxetine-treated animals. In addition, differential gene expressions of cell cycle and death markers were observed. Cyclins D3, E and B were reduced in tumors from animals treated with fluoxetine, whereas the tumor suppressor p53 and the cell cycle inhibitors p15/INK4B, p16/INK4A and p27/Kip1 were increased. Besides, the expression of the antiapoptotic factor Bcl-2 and the proapoptotic factor Bad were lower and higher respectively in these animals. These changes were accompanied by increased IFN-γ and TNF-α levels as well as augmented circulating CD8+ T lymphocytes in tumor-bearing mice treated with the antidepressant. Therefore, we propose that the up-regulation of T-cell mediated antitumor immunity may be contributing to the alterations of tumor cell proliferation and apoptosis thus resulting in the inhibition of tumor progression. © 2011 Elsevier B.V.

Registro:

Documento: Artículo
Título:Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice
Autor:Frick, L.R.; Rapanelli, M.; Arcos, M.L.B.; Cremaschi, G.A.; Genaro, A.M.
Filiación:Centro de Estudios Farmacológicos Y Botánicos, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires (1121), Argentina
Instituto de Biología Y Medicina Experimental, Consejo Nacional de Investigaciones Científicas Y Técnicas, Vuelta de Obligado 2490, Buenos Aires (1428), Argentina
Palabras clave:Antidepressant; Cancer; Fluoxetine; Immunity; Serotonin; caspase 3; cyclin B; cyclin D3; cyclin E; cycline; fluoxetine; gamma interferon; protein BAD; protein bcl 2; protein p15; protein p16; protein p17; protein p53; tumor necrosis factor alpha; animal cell; animal experiment; animal model; apoptosis; article; cancer inhibition; CD8+ T lymphocyte; cell cycle; cell cycle arrest; cell proliferation; cellular immunity; controlled study; female; lymphoma; lymphoma cell; mouse; nonhuman; priority journal; protein expression; treatment outcome; tumor growth; tumor immunity; Administration, Oral; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Fluoxetine; Gene Expression Regulation, Neoplastic; Lymphoma; Mice; Mice, Inbred BALB C; Prognosis; Serotonin Uptake Inhibitors; T-Lymphocytes; Tumor Markers, Biological; Up-Regulation
Año:2011
Volumen:659
Número:2-3
Página de inicio:265
Página de fin:272
DOI: http://dx.doi.org/10.1016/j.ejphar.2011.03.037
Título revista:European Journal of Pharmacology
Título revista abreviado:Eur. J. Pharmacol.
ISSN:00142999
CODEN:EJPHA
CAS:caspase 3, 169592-56-7; fluoxetine, 54910-89-3, 56296-78-7, 59333-67-4; gamma interferon, 82115-62-6; protein bcl 2, 219306-68-0; Fluoxetine, 54910-89-3; Serotonin Uptake Inhibitors; Tumor Markers, Biological
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142999_v659_n2-3_p265_Frick

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Citas:

---------- APA ----------
Frick, L.R., Rapanelli, M., Arcos, M.L.B., Cremaschi, G.A. & Genaro, A.M. (2011) . Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice. European Journal of Pharmacology, 659(2-3), 265-272.
http://dx.doi.org/10.1016/j.ejphar.2011.03.037
---------- CHICAGO ----------
Frick, L.R., Rapanelli, M., Arcos, M.L.B., Cremaschi, G.A., Genaro, A.M. "Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice" . European Journal of Pharmacology 659, no. 2-3 (2011) : 265-272.
http://dx.doi.org/10.1016/j.ejphar.2011.03.037
---------- MLA ----------
Frick, L.R., Rapanelli, M., Arcos, M.L.B., Cremaschi, G.A., Genaro, A.M. "Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice" . European Journal of Pharmacology, vol. 659, no. 2-3, 2011, pp. 265-272.
http://dx.doi.org/10.1016/j.ejphar.2011.03.037
---------- VANCOUVER ----------
Frick, L.R., Rapanelli, M., Arcos, M.L.B., Cremaschi, G.A., Genaro, A.M. Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice. Eur. J. Pharmacol. 2011;659(2-3):265-272.
http://dx.doi.org/10.1016/j.ejphar.2011.03.037