title: Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.
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 proliferation.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hoose
authors.forename: Camille
authors.initials: C
authors.lastname: Duran
authors.forename: Indranil
authors.initials: I
authors.lastname: Malik
authors.forename: Shabnam
authors.initials: S
authors.lastname: Eslamfam
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Shasserre
authors.forename: S Sabina
authors.initials: SS
authors.lastname: Downing
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Hoover
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Dowd
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Polymenis
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D005434:Flow Cytometry; D005473:Fluoxetine / Q000494:pharmacology*; D015248:Gemfibrozil / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects
chemical_list: D005473:Fluoxetine; D015248:Gemfibrozil