title: Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice.
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.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, 1° Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 Piso 15, Buenos Aires (1121), Argentina. lfrick@fmed.uba.ar
authors.forename: Luciana Romina
authors.initials: LR
authors.lastname: Frick
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Rapanelli
authors.forename: Maria Laura Barreiro
authors.initials: ML
authors.lastname: Arcos
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Genaro
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008223:Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011379:Prognosis; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors