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Valproic acid overcomes hypoxia-induced resistance to apoptosis
Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O(2)) conditions only. Therefore, we q...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583540/ https://www.ncbi.nlm.nih.gov/pubmed/22159638 http://dx.doi.org/10.3892/or.2011.1577 |
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author | CIPRO, ŠIMON HŘEBAČKOVÁ, JANA HRABĚTA, JAN POLJAKOVÁ, JITKA ECKSCHLAGER, TOMÁŠ |
author_facet | CIPRO, ŠIMON HŘEBAČKOVÁ, JANA HRABĚTA, JAN POLJAKOVÁ, JITKA ECKSCHLAGER, TOMÁŠ |
author_sort | CIPRO, ŠIMON |
collection | PubMed |
description | Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O(2)) conditions only. Therefore, we questioned whether VPA would be equally effective under hypoxic conditions (1% O(2)), which is known to induce resistance to apoptosis. Four neuroblastoma cell lines were used: UKF-NB-3, SK-N-AS, plus one cisplatin-resistant subline derived from each of the two original sensitive lines. All were treated with VPA and incubated under hypoxic conditions. Measurement of apoptosis and viability using TUNEL assay and Annexin V/propidium iodide labeling revealed that VPA was even more effective under hypoxic conditions. We show here that hypoxia-induced resistance to chemotherapeutic agents such as cisplatin could be overcome using VPA. We also demonstrated that apoptosis pathways induced by VPA do not differ between normoxic and hypoxic conditions. VPA-induced apoptosis proceeds through the mitochondrial pathway, not the extrinsic pathway (under both normoxia and hypoxia), since inhibition of caspase-8 failed to decrease apoptosis or influence bid cleavage. Our data demonstrated that VPA is more efficient in triggering apoptosis under hypoxic conditions and overcomes hypoxia-induced resistance to cisplatin. The results provide additional evidence for the use of VPA in neuroblastoma (NBL) treatment. |
format | Online Article Text |
id | pubmed-3583540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-35835402013-02-28 Valproic acid overcomes hypoxia-induced resistance to apoptosis CIPRO, ŠIMON HŘEBAČKOVÁ, JANA HRABĚTA, JAN POLJAKOVÁ, JITKA ECKSCHLAGER, TOMÁŠ Oncol Rep Articles Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O(2)) conditions only. Therefore, we questioned whether VPA would be equally effective under hypoxic conditions (1% O(2)), which is known to induce resistance to apoptosis. Four neuroblastoma cell lines were used: UKF-NB-3, SK-N-AS, plus one cisplatin-resistant subline derived from each of the two original sensitive lines. All were treated with VPA and incubated under hypoxic conditions. Measurement of apoptosis and viability using TUNEL assay and Annexin V/propidium iodide labeling revealed that VPA was even more effective under hypoxic conditions. We show here that hypoxia-induced resistance to chemotherapeutic agents such as cisplatin could be overcome using VPA. We also demonstrated that apoptosis pathways induced by VPA do not differ between normoxic and hypoxic conditions. VPA-induced apoptosis proceeds through the mitochondrial pathway, not the extrinsic pathway (under both normoxia and hypoxia), since inhibition of caspase-8 failed to decrease apoptosis or influence bid cleavage. Our data demonstrated that VPA is more efficient in triggering apoptosis under hypoxic conditions and overcomes hypoxia-induced resistance to cisplatin. The results provide additional evidence for the use of VPA in neuroblastoma (NBL) treatment. D.A. Spandidos 2011-12-06 2012-04 /pmc/articles/PMC3583540/ /pubmed/22159638 http://dx.doi.org/10.3892/or.2011.1577 Text en Copyright © 2012, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles CIPRO, ŠIMON HŘEBAČKOVÁ, JANA HRABĚTA, JAN POLJAKOVÁ, JITKA ECKSCHLAGER, TOMÁŠ Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title | Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title_full | Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title_fullStr | Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title_full_unstemmed | Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title_short | Valproic acid overcomes hypoxia-induced resistance to apoptosis |
title_sort | valproic acid overcomes hypoxia-induced resistance to apoptosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583540/ https://www.ncbi.nlm.nih.gov/pubmed/22159638 http://dx.doi.org/10.3892/or.2011.1577 |
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