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    
Abstract/OtherAbstract:
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.
Authors:
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    
Affiliation:
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cell Cycle / drug effects*
Cell Proliferation / drug effects
Drug Interactions
Flow Cytometry
Fluoxetine / pharmacology*
Gemfibrozil / pharmacology*
Mitosis / drug effects
Chemical
Reg. No./Substance:
25812-30-0/Gemfibrozil; 54910-89-3/Fluoxetine
Comments/Corrections

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


Previous Document:  Fiscal and policy implications of selling pipe tobacco for roll-your-own cigarettes in the United St...
Next Document:  Transcript profiling identifies dynamic gene expression patterns and an important role for Nrf2/Keap...