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Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment
Aromatase inhibitors (AIs), which block the conversion of androgens to estrogens, are used for hormone-dependent breast cancer treatment. Exemestane, a steroidal that belongs to the third-generation of AIs, is a mechanism-based inhibitor that binds covalently and irreversibly, inactivating and desta...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418278/ https://www.ncbi.nlm.nih.gov/pubmed/22912703 http://dx.doi.org/10.1371/journal.pone.0042398 |
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author | Amaral, Cristina Borges, Margarida Melo, Soraia da Silva, Elisiário Tavares Correia-da-Silva, Georgina Teixeira, Natércia |
author_facet | Amaral, Cristina Borges, Margarida Melo, Soraia da Silva, Elisiário Tavares Correia-da-Silva, Georgina Teixeira, Natércia |
author_sort | Amaral, Cristina |
collection | PubMed |
description | Aromatase inhibitors (AIs), which block the conversion of androgens to estrogens, are used for hormone-dependent breast cancer treatment. Exemestane, a steroidal that belongs to the third-generation of AIs, is a mechanism-based inhibitor that binds covalently and irreversibly, inactivating and destabilizing aromatase. Since the biological effects of exemestane in breast cancer cells are not totally understood, its effects on cell viability, cell proliferation and mechanisms of cell death were studied in an ER-positive aromatase-overexpressing breast cancer cell line (MCF-7aro). The effects of 3-methyladenine (3-MA), an inhibitor of autophagy and of ZVAD-FMK, an apoptotic inhibitor, in exemestane treated cells were also investigated. Our results indicate that exemestane induces a strong inhibition in MCF-7aro cell proliferation in a dose- and time-dependent manner, promoting a significant cell cycle arrest in G(0)/G1 or in G(2)/M phases after 3 and 6 days of treatment, respectively. This was accompanied by a decrease in cell viability due to activation of cell death by apoptosis, via mitochondrial pathway and the occurrence of autophagy. Inhibition of autophagy by the autophagic inhibitor, 3-MA, resulted in a reduction of cell viability and activation of caspases. All together the results obtained suggest that exemestane induced mitochondrial-mediated apoptosis and autophagy, which act as a pro-survival process regulating breast cancer cell apoptosis. |
format | Online Article Text |
id | pubmed-3418278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34182782012-08-21 Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment Amaral, Cristina Borges, Margarida Melo, Soraia da Silva, Elisiário Tavares Correia-da-Silva, Georgina Teixeira, Natércia PLoS One Research Article Aromatase inhibitors (AIs), which block the conversion of androgens to estrogens, are used for hormone-dependent breast cancer treatment. Exemestane, a steroidal that belongs to the third-generation of AIs, is a mechanism-based inhibitor that binds covalently and irreversibly, inactivating and destabilizing aromatase. Since the biological effects of exemestane in breast cancer cells are not totally understood, its effects on cell viability, cell proliferation and mechanisms of cell death were studied in an ER-positive aromatase-overexpressing breast cancer cell line (MCF-7aro). The effects of 3-methyladenine (3-MA), an inhibitor of autophagy and of ZVAD-FMK, an apoptotic inhibitor, in exemestane treated cells were also investigated. Our results indicate that exemestane induces a strong inhibition in MCF-7aro cell proliferation in a dose- and time-dependent manner, promoting a significant cell cycle arrest in G(0)/G1 or in G(2)/M phases after 3 and 6 days of treatment, respectively. This was accompanied by a decrease in cell viability due to activation of cell death by apoptosis, via mitochondrial pathway and the occurrence of autophagy. Inhibition of autophagy by the autophagic inhibitor, 3-MA, resulted in a reduction of cell viability and activation of caspases. All together the results obtained suggest that exemestane induced mitochondrial-mediated apoptosis and autophagy, which act as a pro-survival process regulating breast cancer cell apoptosis. Public Library of Science 2012-08-13 /pmc/articles/PMC3418278/ /pubmed/22912703 http://dx.doi.org/10.1371/journal.pone.0042398 Text en © 2012 Amaral et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Amaral, Cristina Borges, Margarida Melo, Soraia da Silva, Elisiário Tavares Correia-da-Silva, Georgina Teixeira, Natércia Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title | Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title_full | Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title_fullStr | Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title_full_unstemmed | Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title_short | Apoptosis and Autophagy in Breast Cancer Cells following Exemestane Treatment |
title_sort | apoptosis and autophagy in breast cancer cells following exemestane treatment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418278/ https://www.ncbi.nlm.nih.gov/pubmed/22912703 http://dx.doi.org/10.1371/journal.pone.0042398 |
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