7-Ketocholesterol and cholestane-triol increase expression of SMO and LXR? signaling pathways in a human breast cancer cell line.

ABSTRACT: 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-3?-5?-6?-triol (triol), and a mixture of 5?-cholestane-3?,6?-diol and 5?-cholestane-3?,6?-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 LXR?, 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 LXR? pathways might be involved in the apoptotic process promoted by 7-KC and triol.

SUBMITTER: Levy D 

PROVIDER: S-EPMC6709374 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature