Oxysterols in cell viability, phospholipidosis and extracellular vesicles production

The study carried out systematic research on the influence of selected oxysterols on cells viability, phospholipidosis and the level of secreted extracellular vesicles. Three oxidized cholesterol derivatives, namely 7α-hydroxycholesterol (7α-OH), 7- ketocholesterol (7-K) and 24-hydroxycholesterol (24-OH) were tested in three different concentrations: 50 μM, 100 μM and 200 μM for 24 hours incubation with A549 lung cancer cell line. All the studied oxysterols were found to alter cells viability. The lowest survival rate of the cells was observed after 24 h of 7-K treatment. Cells incubated with 24-OH had the best survival rate of all oxysterols used. 7-K increased phospholipids accumulation in cells but the strongest effect was observed for 24-OH. Changes in the level of extracellular vesicles secreted in cells culture were also observed. It was found that all oxysterols used increased the level of secreted vesicles, both exosomes and ectosomes. The strongest effect was noticed for 24-OH. Taken together, these results suggest that 7-K and 7α-OH are the most potent inducers of cancer cell death. The lower cytotoxic effect of 24-OH correlates with greater phospholipids accumulation, extracellular vesicles production and better cells survival.