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

Autor(es)

Levy, Debora ; de Melo, Thatiana Correa ; Oliveira, Beatriz A. ; Paz, Jessica L. ; de Freitas, Fabio A. ; Reichert, Cadiele O. ; Rodrigues, Alessandro ; Bydlowski, Sergio P.

• Tipo de documento: Artigo Científico
• Fonte: BIOCHEMISTRY AND BIOPHYSICS REPORTS; v. 19, p. 6-pg., 2019-09-01.

Resumo

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 beta-5 alpha-6 beta-triol (triol), and a mixture of 5 alpha-cholestane-3 beta,6 alpha-diol and 5a-cholestane-3j3,6a-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 alpha, 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 alpha pathways might be involved in the apoptotic process promoted by 7-KC and triol. (AU)

• Processo FAPESP: 13/10073-5 - Catálise orgânica: planejamento, síntese e aplicações em reações orgânicas estereosseletivas
• Beneficiário: Alessandro Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/21676-0 - Reações de haloaminação enantiosseletivas visando a síntese de aminodióis
• Beneficiário: Alessandro Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular