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Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells

Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a “first-generation” antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in...

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Autores principales: Papadopoulos, Fotios, Isihou, Rafaela, Alexiou, George A., Tsalios, Thomas, Vartholomatos, Evrysthenis, Markopoulos, Georgios S., Sioka, Chrissa, Tsekeris, Pericles, Kyritsis, Athanasios P., Galani, Vasiliki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763579/
https://www.ncbi.nlm.nih.gov/pubmed/33322363
http://dx.doi.org/10.3390/biomedicines8120595
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author Papadopoulos, Fotios
Isihou, Rafaela
Alexiou, George A.
Tsalios, Thomas
Vartholomatos, Evrysthenis
Markopoulos, Georgios S.
Sioka, Chrissa
Tsekeris, Pericles
Kyritsis, Athanasios P.
Galani, Vasiliki
author_facet Papadopoulos, Fotios
Isihou, Rafaela
Alexiou, George A.
Tsalios, Thomas
Vartholomatos, Evrysthenis
Markopoulos, Georgios S.
Sioka, Chrissa
Tsekeris, Pericles
Kyritsis, Athanasios P.
Galani, Vasiliki
author_sort Papadopoulos, Fotios
collection PubMed
description Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a “first-generation” antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in glioblastoma (GBM) U87, U251 and T98 cell lines, and the effects of combined treatment with temozolomide (TMZ) and/or radiotherapy, using 4 Gy of irradiation. The viability and proliferation of the cells were evaluated with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, using the annexin-propidium iodide (PI), and cell cycle, cluster of differentiation (CD) expression and caspase-8 activation were measured using flow cytometry. Treatment with haloperidol significantly reduced cell viability in U87, U251 and T98 GBM cell lines. Haloperidol induced apoptosis in a dose-dependent manner, inhibited cell migration and produced an alteration in the expression of CD24/CD44. The additional effect of haloperidol, combined with temozolomide and radiation therapy, increased tumor cell death. Haloperidol was observed to induce apoptosis and to increase caspase-8 activation. In conclusion, haloperidol may represent an innovative strategy for the treatment of GBM and further studies are warranted in glioma xenograft models and other malignancies.
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spelling pubmed-77635792020-12-27 Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells Papadopoulos, Fotios Isihou, Rafaela Alexiou, George A. Tsalios, Thomas Vartholomatos, Evrysthenis Markopoulos, Georgios S. Sioka, Chrissa Tsekeris, Pericles Kyritsis, Athanasios P. Galani, Vasiliki Biomedicines Article Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a “first-generation” antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in glioblastoma (GBM) U87, U251 and T98 cell lines, and the effects of combined treatment with temozolomide (TMZ) and/or radiotherapy, using 4 Gy of irradiation. The viability and proliferation of the cells were evaluated with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, using the annexin-propidium iodide (PI), and cell cycle, cluster of differentiation (CD) expression and caspase-8 activation were measured using flow cytometry. Treatment with haloperidol significantly reduced cell viability in U87, U251 and T98 GBM cell lines. Haloperidol induced apoptosis in a dose-dependent manner, inhibited cell migration and produced an alteration in the expression of CD24/CD44. The additional effect of haloperidol, combined with temozolomide and radiation therapy, increased tumor cell death. Haloperidol was observed to induce apoptosis and to increase caspase-8 activation. In conclusion, haloperidol may represent an innovative strategy for the treatment of GBM and further studies are warranted in glioma xenograft models and other malignancies. MDPI 2020-12-11 /pmc/articles/PMC7763579/ /pubmed/33322363 http://dx.doi.org/10.3390/biomedicines8120595 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papadopoulos, Fotios
Isihou, Rafaela
Alexiou, George A.
Tsalios, Thomas
Vartholomatos, Evrysthenis
Markopoulos, Georgios S.
Sioka, Chrissa
Tsekeris, Pericles
Kyritsis, Athanasios P.
Galani, Vasiliki
Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title_full Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title_fullStr Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title_full_unstemmed Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title_short Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
title_sort haloperidol induced cell cycle arrest and apoptosis in glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763579/
https://www.ncbi.nlm.nih.gov/pubmed/33322363
http://dx.doi.org/10.3390/biomedicines8120595
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