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A more recent version of this article appeared on May 1, 2005

Papers In Press, published online ahead of print February 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400407-JLR200
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Submitted on October 15, 2004
Revised on January 24, 2005
Accepted on February 1, 2005

Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression

Carlos Fernández, Miguel Martín, Diego Gómez-Coronado, and Miguel A. Lasunción

Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal and Universidad de Alcalá, Madrid 28034

Corresponding Author: miguel.a.lasuncion{at}hrc.es

Cholesterol is a major lipid component of the plasma membrane in animal cells. In addition to its structural requirement, cholesterol is essential in cell proliferation and other cell processes. The aim of the present study was to elucidate the stringency of the requirement for cholesterol as a regulator of proliferation and cell cycle progression, as compared to other sterols of the cholesterol biosynthesis pathway. The human promyelocytic HL-60 cells were cultured in cholesterol-free medium and treated with different distal inhibitors of cholesterol biosynthesis (zaragozic acid, SKF 104976, SR 31747, BM 15766 and AY 9944) which allow the synthesis of isoprenoid derivatives and different sets of sterol intermediates, but not cholesterol. The results showed that only the inhibition of sterol delta 7-reductase was compatible with cell proliferation. Blocking cholesterol biosynthesis upstream this enzyme resulted in the inhibition of cell proliferation and cell cycle arrest selectively in G2/M phase.


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