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Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity

BACKGROUND: Estrogen receptor (ER) β acts as a tumor suppressor in malignant mesotheliomas. METHODS: Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERβ agonist, KB9520, in human mesothelioma cell lines in vitro and in a mesothelioma mouse model in vivo. RESULT...

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Autores principales: Pinton, Giulia, Manente, Arcangela G, Daga, Antonio, Cilli, Michele, Rinaldi, Maurizio, Nilsson, Stefan, Moro, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197308/
https://www.ncbi.nlm.nih.gov/pubmed/25277603
http://dx.doi.org/10.1186/1476-4598-13-227
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author Pinton, Giulia
Manente, Arcangela G
Daga, Antonio
Cilli, Michele
Rinaldi, Maurizio
Nilsson, Stefan
Moro, Laura
author_facet Pinton, Giulia
Manente, Arcangela G
Daga, Antonio
Cilli, Michele
Rinaldi, Maurizio
Nilsson, Stefan
Moro, Laura
author_sort Pinton, Giulia
collection PubMed
description BACKGROUND: Estrogen receptor (ER) β acts as a tumor suppressor in malignant mesotheliomas. METHODS: Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERβ agonist, KB9520, in human mesothelioma cell lines in vitro and in a mesothelioma mouse model in vivo. RESULTS: KB9520 showed significant anti-proliferative effect in ERβ positive human malignant pleural mesothelioma cells in vitro. Selective activation of ERβ with KB9520 sensitized the cells to treatment with cisplatin, resulting in enhanced growth inhibition and increased apoptosis. Furthermore, in CD1 nude mice mesothelioma tumor growth was significantly inhibited when KB9520 was added on top of the standard of care chemo combination cisplatin/pemetrexed, as compared to the cisplatin/pemetrexed alone group. Importantly, KB9520 exerted a protective effect to cisplatin toxicity in the non-malignant mesothelium derived MET5A cells. CONCLUSIONS: Together, the data presented suggest that selective targeting of ERβ may be an efficacious stand-alone treatment option and/or become an important add-on to existing malignant mesothelioma therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-4598-13-227) contains supplementary material, which is available to authorized users.
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spelling pubmed-41973082014-10-16 Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity Pinton, Giulia Manente, Arcangela G Daga, Antonio Cilli, Michele Rinaldi, Maurizio Nilsson, Stefan Moro, Laura Mol Cancer Research BACKGROUND: Estrogen receptor (ER) β acts as a tumor suppressor in malignant mesotheliomas. METHODS: Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERβ agonist, KB9520, in human mesothelioma cell lines in vitro and in a mesothelioma mouse model in vivo. RESULTS: KB9520 showed significant anti-proliferative effect in ERβ positive human malignant pleural mesothelioma cells in vitro. Selective activation of ERβ with KB9520 sensitized the cells to treatment with cisplatin, resulting in enhanced growth inhibition and increased apoptosis. Furthermore, in CD1 nude mice mesothelioma tumor growth was significantly inhibited when KB9520 was added on top of the standard of care chemo combination cisplatin/pemetrexed, as compared to the cisplatin/pemetrexed alone group. Importantly, KB9520 exerted a protective effect to cisplatin toxicity in the non-malignant mesothelium derived MET5A cells. CONCLUSIONS: Together, the data presented suggest that selective targeting of ERβ may be an efficacious stand-alone treatment option and/or become an important add-on to existing malignant mesothelioma therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-4598-13-227) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-02 /pmc/articles/PMC4197308/ /pubmed/25277603 http://dx.doi.org/10.1186/1476-4598-13-227 Text en © Pinton et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Pinton, Giulia
Manente, Arcangela G
Daga, Antonio
Cilli, Michele
Rinaldi, Maurizio
Nilsson, Stefan
Moro, Laura
Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title_full Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title_fullStr Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title_full_unstemmed Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title_short Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
title_sort agonist activation of estrogen receptor beta (erβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197308/
https://www.ncbi.nlm.nih.gov/pubmed/25277603
http://dx.doi.org/10.1186/1476-4598-13-227
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