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

Research output: Contribution to journalArticle

Authors

  • Marwan Ibrahim Abdullah
  • Mohammed Najim Abed
  • Farhat Khanim
  • Alan Richardson

Colleges, School and Institutes

External organisations

  • Keele University
  • Al-Salam Teaching Hospital
  • University of Mosul

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.

Details

Original languageEnglish
Article number9632
JournalScientific Reports
Volume9
Issue number1
Publication statusPublished - 1 Dec 2019

ASJC Scopus subject areas