As an essential component of mammalian cell membranes, cells require
cholesterol for proliferation, which is either obtained from plasma
lipoproteins or synthesized intracellularly from
acetyl-CoA. In addition to
cholesterol, other non-
sterol mevalonate derivatives are necessary for
DNA synthesis, such as the phosphorylated forms of
isopentane,
farnesol,
geranylgeraniol, and
dolichol. The aim of the present study was to elucidate the role of
cholesterol in mitosis. For this, human
leukemia cells (HL-60) were incubated in a
cholesterol-free medium and treated with
SKF 104976, which inhibits
cholesterol biosynthesis by blocking
sterol 14alpha-demethylase, and the expression of relevant
cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged
cholesterol starvation induced the inhibition of cytokinesis and the formation of
polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with
cholesterol completely abolished these effects, demonstrating they were specifically due to
cholesterol deficiency. This is the first evidence that
cholesterol is essential for mitosis completion and that, in the absence of
cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher
DNA ploidy (
tetraploidy), and then progressed through S (rereplication) into G2, generating
polyploid cells.