Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression.
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, compared with other sterols of the cholesterol biosynthesis pathway. 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 Delta7-reductase was compatible with cell proliferation. Blocking cholesterol biosynthesis upstream of this enzyme resulted in the inhibition of cell proliferation and cell cycle arrest selectively in G2/M phase.
Fernández
Carlos
C
Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal, 28034 Madrid, Spain.
Martín
Miguel
M
Gómez-Coronado
Diego
D
Lasunción
Miguel A
MA
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002784:Cholesterol / Q000096:biosynthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018922:HL-60 Cells; D006801:Humans
D000924:Anticholesteremic Agents; D002784:Cholesterol