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
7-ketocholesterol (7-KC), cholestane-3β-5α-6β-triol (triol), and a mixture of 5α-cholestane-3β,6β-diol and 5α-cholestane-3β,6α-diol (diol) to promote cell death in a human
breast cancer cell line (MDA-MB-231). We determined cell viability, after 24-h incubation with
oxysterols. These
oxysterols promoted apoptosis. At least part of the observed effects promoted by 7-KC and triol arose from an increase in the expression of the sonic hedgehog pathway mediator, smoothened. However, this increased expression was apparently independent of sonic hedgehog expression, which did not change. Moreover, these
oxysterols led to increased expression of LXRα, which is involved in cellular
cholesterol efflux, and the
ATP-binding cassette transporters, ABCA1 and ABCG1. Diols did not affect these pathways. These results suggested that the sonic hedgehog and LXRα pathways might be involved in the apoptotic process promoted by 7-KC and triol.