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The Cell Killing Mechanisms of Hydroxyurea

Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative...

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Autores principales: Singh, Amanpreet, Xu, Yong-Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126785/
https://www.ncbi.nlm.nih.gov/pubmed/27869662
http://dx.doi.org/10.3390/genes7110099
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author Singh, Amanpreet
Xu, Yong-Jie
author_facet Singh, Amanpreet
Xu, Yong-Jie
author_sort Singh, Amanpreet
collection PubMed
description Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause. Recent studies in multiple model organisms have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea. This review aims to summarize the progress in our understanding of the cell-killing mechanisms of hydroxyurea, which may provide new insights towards the improvement of chemotherapies that employ this agent.
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spelling pubmed-51267852016-12-02 The Cell Killing Mechanisms of Hydroxyurea Singh, Amanpreet Xu, Yong-Jie Genes (Basel) Review Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause. Recent studies in multiple model organisms have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea. This review aims to summarize the progress in our understanding of the cell-killing mechanisms of hydroxyurea, which may provide new insights towards the improvement of chemotherapies that employ this agent. MDPI 2016-11-17 /pmc/articles/PMC5126785/ /pubmed/27869662 http://dx.doi.org/10.3390/genes7110099 Text en © 2016 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 Review
Singh, Amanpreet
Xu, Yong-Jie
The Cell Killing Mechanisms of Hydroxyurea
title The Cell Killing Mechanisms of Hydroxyurea
title_full The Cell Killing Mechanisms of Hydroxyurea
title_fullStr The Cell Killing Mechanisms of Hydroxyurea
title_full_unstemmed The Cell Killing Mechanisms of Hydroxyurea
title_short The Cell Killing Mechanisms of Hydroxyurea
title_sort cell killing mechanisms of hydroxyurea
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126785/
https://www.ncbi.nlm.nih.gov/pubmed/27869662
http://dx.doi.org/10.3390/genes7110099
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