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Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death

Abed, M; Khanim, F; Richardson, A; Abdullah, M

Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death Thumbnail


Authors

M Abed

F Khanim

M Abdullah



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.

Acceptance Date Jun 28, 2019
Publication Date Jul 3, 2019
Publicly Available Date Mar 28, 2024
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
DOI https://doi.org/10.1038/s41598-019-46102-1
Keywords Pitavastatin, prednisolone, ovarian cancer, drug combination, drug repositioning, mevalonate pathway
Publisher URL https://www.nature.com/srep/

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