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Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death
The survival rate for patients with ovarian cancer has changed little in the past three decades since the introduction of platinum-based chemotherapy and new drugs are needed. Statins are drugs used for the treatment and prevention of cardiovascular diseases. Recent work from our laboratory has show...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610640/ https://www.ncbi.nlm.nih.gov/pubmed/31270377 http://dx.doi.org/10.1038/s41598-019-46102-1 |
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author | Abdullah, Marwan Ibrahim Abed, Mohammed Najim Khanim, Farhat Richardson, Alan |
author_facet | Abdullah, Marwan Ibrahim Abed, Mohammed Najim Khanim, Farhat Richardson, Alan |
author_sort | Abdullah, Marwan Ibrahim |
collection | PubMed |
description | The survival rate for patients with ovarian cancer has changed little in the past three decades since the introduction of platinum-based chemotherapy and new drugs are needed. Statins are drugs used for the treatment and prevention of cardiovascular diseases. Recent work from our laboratory has shown that pitavastatin has potential as a treatment for ovarian cancer if dietary geranylgeraniol is controlled. However, relatively high doses of statins are required to induce apoptosis in cancer cells, increasing the risk of myopathy, the most common adverse effect associated with statins. This makes it desirable to identify drugs which reduce the dose of pitavastatin necessary to treat cancer. A drug-repositioning strategy was employed to identify suitable candidates. Screening a custom library of 100 off-patent drugs for synergistic activity with pitavastatin identified prednisolone as the most prominent hit. Prednisolone potentiated the activity of pitavastatin in several assays measuring the growth, survival or apoptosis in several ovarian cancer cells lines. Prednisolone, alone or in some cases in combination with pitavastatin, reduced the expression of genes encoding enzymes in the mevalonate pathway, providing a mechanistic explanation for the synergy. |
format | Online Article Text |
id | pubmed-6610640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66106402019-07-15 Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death Abdullah, Marwan Ibrahim Abed, Mohammed Najim Khanim, Farhat Richardson, Alan Sci Rep Article The survival rate for patients with ovarian cancer has changed little in the past three decades since the introduction of platinum-based chemotherapy and new drugs are needed. Statins are drugs used for the treatment and prevention of cardiovascular diseases. Recent work from our laboratory has shown that pitavastatin has potential as a treatment for ovarian cancer if dietary geranylgeraniol is controlled. However, relatively high doses of statins are required to induce apoptosis in cancer cells, increasing the risk of myopathy, the most common adverse effect associated with statins. This makes it desirable to identify drugs which reduce the dose of pitavastatin necessary to treat cancer. A drug-repositioning strategy was employed to identify suitable candidates. Screening a custom library of 100 off-patent drugs for synergistic activity with pitavastatin identified prednisolone as the most prominent hit. Prednisolone potentiated the activity of pitavastatin in several assays measuring the growth, survival or apoptosis in several ovarian cancer cells lines. Prednisolone, alone or in some cases in combination with pitavastatin, reduced the expression of genes encoding enzymes in the mevalonate pathway, providing a mechanistic explanation for the synergy. Nature Publishing Group UK 2019-07-03 /pmc/articles/PMC6610640/ /pubmed/31270377 http://dx.doi.org/10.1038/s41598-019-46102-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Abdullah, Marwan Ibrahim Abed, Mohammed Najim Khanim, Farhat Richardson, Alan Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title | Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title_full | Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title_fullStr | Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title_full_unstemmed | Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title_short | Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
title_sort | screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610640/ https://www.ncbi.nlm.nih.gov/pubmed/31270377 http://dx.doi.org/10.1038/s41598-019-46102-1 |
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