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Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line

The treatment of solid cancers with pharmacological all-trans retinoic acid (ATRA) concentrations, even if it is a gold standard therapy for the acute promyelocytic leukaemia (APL), is not always effective due to some resistance mechanisms. Here the resistance to ATRA treatment of T24 cell line, bla...

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Autores principales: Costantini, Lara, Molinari, Romina, Farinon, Barbara, Lelli, Veronica, Timperio, Anna Maria, Merendino, Nicolò
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465316/
https://www.ncbi.nlm.nih.gov/pubmed/32756427
http://dx.doi.org/10.3390/jcm9082494
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author Costantini, Lara
Molinari, Romina
Farinon, Barbara
Lelli, Veronica
Timperio, Anna Maria
Merendino, Nicolò
author_facet Costantini, Lara
Molinari, Romina
Farinon, Barbara
Lelli, Veronica
Timperio, Anna Maria
Merendino, Nicolò
author_sort Costantini, Lara
collection PubMed
description The treatment of solid cancers with pharmacological all-trans retinoic acid (ATRA) concentrations, even if it is a gold standard therapy for the acute promyelocytic leukaemia (APL), is not always effective due to some resistance mechanisms. Here the resistance to ATRA treatment of T24 cell line, bladder cancer, was investigated. T24 was not only resistant to cell death when treated at concentrations up to 20 µM of ATRA, but it was also able to stimulate the cellular proliferation. An over-expression of the fatty acid binding protein 5 (FABP5) in conjunction with the cellular retinol-binding protein-II (CRABP-II) down-expression was found. However, the direct inhibition of the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) did not abolish T24 proliferation, but rather potentiated it. Moreover, considering the ability of the long-chain fatty acids (LCFAs) to displace ATRA from FABP5, the actions of the saturated palmitic acid (PA), unsaturated omega-6 linoleic acid (LA) and omega-3 docosahexaenoic acid (DHA) were evaluated to counteract ATRA-related proliferation. ATRA-PA co-treatment induces cellular growth inhibition, while ATRA-LA co-treatment induces cellular growth enhancement. However, even if DHA is unsaturated LCFA as LA, it was able to reverse the ATRA-induced cellular proliferation of T24, bringing the viability percentages at the levels of the control.
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spelling pubmed-74653162020-09-04 Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line Costantini, Lara Molinari, Romina Farinon, Barbara Lelli, Veronica Timperio, Anna Maria Merendino, Nicolò J Clin Med Article The treatment of solid cancers with pharmacological all-trans retinoic acid (ATRA) concentrations, even if it is a gold standard therapy for the acute promyelocytic leukaemia (APL), is not always effective due to some resistance mechanisms. Here the resistance to ATRA treatment of T24 cell line, bladder cancer, was investigated. T24 was not only resistant to cell death when treated at concentrations up to 20 µM of ATRA, but it was also able to stimulate the cellular proliferation. An over-expression of the fatty acid binding protein 5 (FABP5) in conjunction with the cellular retinol-binding protein-II (CRABP-II) down-expression was found. However, the direct inhibition of the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) did not abolish T24 proliferation, but rather potentiated it. Moreover, considering the ability of the long-chain fatty acids (LCFAs) to displace ATRA from FABP5, the actions of the saturated palmitic acid (PA), unsaturated omega-6 linoleic acid (LA) and omega-3 docosahexaenoic acid (DHA) were evaluated to counteract ATRA-related proliferation. ATRA-PA co-treatment induces cellular growth inhibition, while ATRA-LA co-treatment induces cellular growth enhancement. However, even if DHA is unsaturated LCFA as LA, it was able to reverse the ATRA-induced cellular proliferation of T24, bringing the viability percentages at the levels of the control. MDPI 2020-08-03 /pmc/articles/PMC7465316/ /pubmed/32756427 http://dx.doi.org/10.3390/jcm9082494 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
Costantini, Lara
Molinari, Romina
Farinon, Barbara
Lelli, Veronica
Timperio, Anna Maria
Merendino, Nicolò
Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title_full Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title_fullStr Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title_full_unstemmed Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title_short Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line
title_sort docosahexaenoic acid reverted the all-trans retinoic acid-induced cellular proliferation of t24 bladder cancer cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465316/
https://www.ncbi.nlm.nih.gov/pubmed/32756427
http://dx.doi.org/10.3390/jcm9082494
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