systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine系统分析的常用药物会导致细胞周期的影响的发现抑制二甲苯氧庚酸之间的交互和氟西汀.pdf

Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine 1 1 1 1 1 Scott A. Hoose , Camille Duran , Indranil Malik , Shabnam Eslamfam , Samantha C. Shasserre , S. 1 1 1 2 1 Sabina Downing , Evelyn M. Hoover , Katherine E. Dowd , Roger Smith III , Michael Polymenis * 1 Department of Biochemistry and Biophysics, Texas AM University, College Station, Texas, United States of America, 2 Department of Veterinary Pathobiology, Texas AM University, College Station, Texas, United States of America 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