Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 169, Issue -, Pages 164-175Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2016.04.017
Keywords
Oxysterol; Mesenchymal stem cell; Apoptosis; Cell death; Mitochondrial hyperpolarization; Adipose tissue
Funding
- Financiadora de Estudos e Projetos (FINEP), Brazil
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
- Institute Nacional de Ciencia e Tecnologia - Fluidos Complexos (INCT-FCx), Brazil
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Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Potent effects in cell death processes, including cytoxicity and apoptosis induction, were described in several cell lines. Very little is known about the effects of oxysterols in MSCs. 7-ketocholesterol (7-KC), one of the most important oxysterols, was shown to be cytotoxic to human adipose tissue-derived MSCs. Here, we describe the short-term (24 h) cytotoxic effects of cholestan-3 alpha-5 beta-6 alpha-triol, 3,5 cholestan-7-one, (3 alpha-5 beta-6 alpha)- cholestane-3,6-diol, 7-oxocholest-5-en-3 beta-ylacetate, and 5 beta-6 beta epoxy-cholesterol, on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from three young, healthy women. Oxysterols, with the exception of 3,5 cholestan-7-one and 7-oxocholest-5-en-3 beta-yl acetate, led to a complex mode of cell death that include apoptosis, necrosis and autophagy, depending on the type of oxysterol and concentration, being cholestan-3 alpha-5 beta-6 alpha-triol the most effective. Inhibition of proliferation was also promoted by these oxysterols, but no changes in cell cycle were observed. (C) 2016 Elsevier Ltd. All rights reserved.
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