Abdullah, M, Abed, M, Khanim, F and Richardson, A ORCID: https://orcid.org/0000-0003-1825-3375 (2019) Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death. Scientific Reports, 9 (9632).

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Abstract

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.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Nature Publishing Group at https://doi.org/10.1038/s41598-019-46102-1 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Pitavastatin, prednisolone, ovarian cancer, drug combination, drug repositioning, mevalonate pathway
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy
Depositing User: Symplectic
Date Deposited: 28 Jun 2019 10:40
Last Modified: 24 Jul 2019 08:37
URI: http://eprints.keele.ac.uk/id/eprint/6541

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