Document Detail

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.
MedLine Citation:
PMID:  22567160     Owner:  NLM     Status:  MEDLINE    
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 proliferation.
Scott A Hoose; Camille Duran; Indranil Malik; Shabnam Eslamfam; Samantha C Shasserre; S Sabina Downing; Evelyn M Hoover; Katherine E Dowd; Roger Smith; Michael Polymenis
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-05-02
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-05-08     Completed Date:  2012-09-17     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e36503     Citation Subset:  IM    
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.
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MeSH Terms
Cell Cycle / drug effects*
Cell Proliferation / drug effects
Drug Interactions
Flow Cytometry
Fluoxetine / pharmacology*
Gemfibrozil / pharmacology*
Mitosis / drug effects
Reg. No./Substance:
25812-30-0/Gemfibrozil; 54910-89-3/Fluoxetine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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