Oxysterol-induced apoptosis in human monocytic cell lines

Oxysterols constitute a large family of natural compounds, endowed with various biological activities including cholesterol regulation, immunosuppression and antitumoral potency. In the present study, we examine and compare the cytotoxic effects of two representative members of this family: 7 beta-hydroxycholesterol (7 beta-OH) and 25-hydroxycholesterol (25-OH), in two human monocytic cell lines, U-937 and HL-60. In both cell lines 7 beta-OH at 30 mu M induces cell death by apoptosis within the first hours of treatment. Under the same conditions and in contrast with results previously obtained with lymphoma cells, 25-OH is cytostatic only. It is interesting to note that the simultaneous treatment of U-937 cells by equimolar concentrations of 7 beta-OH and 25-OH leads to a considerably decreased induction of apoptosis. Such an effect is not observed with HL-60 cells. Taken together, these results indicate for the first time that: 1) oxysterols hydroxylated on the sterol nucleus are also able to induce apoptosis, 2) apoptosis can be induced by these substances in cells belonging to the myeloid lineage and 3) as far as apoptosis is concerned, a combined treatment with 7 beta-OH and 25-OH can lead to opposite effects depending on the cell type.