Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice
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 fluoxe...
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todo:paper_00142999_v659_n2-3_p265_Frick2023-10-03T14:12:09Z Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice Frick, L.R. Rapanelli, M. Arcos, M.L.B. Cremaschi, G.A. Genaro, A.M. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00142999_v659_n2-3_p265_Frick |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 |
spellingShingle |
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 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 |
topic_facet |
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 |
description |
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. |
format |
JOUR |
author |
Frick, L.R. Rapanelli, M. Arcos, M.L.B. Cremaschi, G.A. Genaro, A.M. |
author_facet |
Frick, L.R. Rapanelli, M. Arcos, M.L.B. Cremaschi, G.A. Genaro, A.M. |
author_sort |
Frick, L.R. |
title |
Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice |
title_short |
Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice |
title_full |
Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice |
title_fullStr |
Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice |
title_full_unstemmed |
Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice |
title_sort |
oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates t cell immunity in tumor-bearing mice |
url |
http://hdl.handle.net/20.500.12110/paper_00142999_v659_n2-3_p265_Frick |
work_keys_str_mv |
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