Oxysterols selectively promote short-term apoptosis in tumor cell lines

Highlights: • Several cholesterol oxides were evaluated for their capacity to induce cell death. • Short-term cytotoxicity of oxysterols varied with their type and concentration. • Short-term cytotoxicity of oxysterols varied with the cell lineage. • Cytotoxic oxysterols induced apoptosis in human breast cancer and mouse melanoma. • They also inhibited the S phase and stimulated either the G0/G1 or the G2/M phase. Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of several oxysterols to induce short-term death in cancerous (human breast cancer and mouse skin melanoma cells) and non-cancerous (human endothelial cells and lung fibroblasts) cell lines. We determined cell viability, Ki67 expression, cell cycle regulation, and apoptosis after 24-h incubations with oxysterols. We found that different oxysterols had different effects on the studied parameters. Moreover, the effects depended on cell type and oxysterol concentration. Three cytotoxic oxysterols (7-ketocholesterol, cholestane-3β-5α-6β-triol, and 5α-cholestane-3β,6β-diol) inhibited the S phase and stimulated the G0/G1 or G2/M phases. These oxysterols promoted apoptosis, determined with Annexin V and propidium iodide assays. These results showed that different oxysterols have cytotoxic effects depending on the cell line. The findings suggest a potential pharmacological utility of cytotoxic oxysterols.