Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

PloS One
Scott A HooseM Polymenis

Abstract

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell pro...Continue Reading

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Citations

Dec 22, 2015·Cell Reports·Teemu P Miettinen, Mikael Björklund
May 30, 2020·Nature Reviews. Drug Discovery·Linda PartridgeBrian K Kennedy
Aug 22, 2018·International Journal of Molecular Sciences·Fatima MaqoudDomenico Tricarico
Apr 10, 2021·Asian Journal of Psychiatry·Pravallika ManjappaReeteka Sud

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Methods Mentioned

BETA
flow
flow cytometry

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CellQuest
FlowJo
Accucomp Beckman
Excel

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