CHOLESTEROL, BUT NOT ITS ESTERS, TRIGGERS PROGRAMMED CELL-DEATH IN HUMAN ERYTHROLEUKEMIA K562 CELLS

Cholesterol, its biosynthetic precursors and the cholesterol-lowering drug compactin were able to inhibit the growth of human erythroleukemi a K562 cells. Compactin, farnesyldiphosphate and cholesterol were cyto toxic by the induction of apoptosis (programmed cell death, PCD). Comp actin doubled the number of apoptotic cells compared to control number s, whereas farnesyldiphosphate and cholesterol led to a fivefold incre ase in PCD over the control levels. At variance with cholesterol, chol esterol esters did not affect K562 cell viability and apoptotic body f ormation, regardless of chain length and degree of saturation. Compact in and farnesyldiphosphate reduced the membrane cholesterol content, t hus increasing membrane fluidity. Conversely, cholesterol treatment re duced the membrane fluidity by increasing cholesterol content in the l ipid bilayer. Unlike farnesyldiphosphate, the other cholesterol precur sors and cholesterol esters were ineffective in increasing the cholest erol content and, thereby, the fluidity of cell membranes. Compactin a nd cholesterol precursors, apart from farnesyldiphosphate, did not aff ect the amount of the farnesylated proteins Pas and lamin B in the cyt osolic and the membrane fractions of K562 cell extracts, whereas farne syldiphosphate reduced the content of both proteins in both fractions. The level of lamin B in K562 cytosol and membranes was also reduced b y cholesterol treatment, which did not significantly affect the amount of Ras. These findings highlight the role of cholesterol in promoting PCD.