Oxysterols selectively promote short-term apoptosis in tumor cell lines

• Published in: Biochemical and biophysical research communications Vol. 505; no. 4; pp. 1043 - 1049
• Main Authors: Levy, Debora, Correa de Melo, Thatiana, Ohira, Bianca Yumi, Fidelis, Maíra Luísa, Ruiz, Jorge L.M., Rodrigues, Alessandro, Bydlowski, Sergio P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.11.2018
• Subjects: 60 APPLIED LIFE SCIENCES; Annexin V; Apoptosis; Apoptosis - drug effects; Cancer; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; CHOLESTEROL; Dose-Response Relationship, Drug; FIBROBLASTS; HUMAN POPULATIONS; Humans; KI67; MAMMARY GLANDS; MELANOMAS; MICE; Oxysterol; Oxysterols - pharmacology; Structure-Activity Relationship; TUMOR CELLS; Annexin V; KI67; Oxysterol; Apoptosis; Cancer
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.10.008

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 several oxysterols to induce short-term death in cancerous (human breast cancer and mouse skin melanoma cells) and non-cancerous (human endothelial cells and lung fibroblasts) cell lines. We determined cell viability, Ki67 expression, cell cycle regulation, and apoptosis after 24-h incubations with oxysterols. We found that different oxysterols had different effects on the studied parameters. Moreover, the effects depended on cell type and oxysterol concentration. Three cytotoxic oxysterols (7-ketocholesterol, cholestane-3β-5α-6β-triol, and 5α-cholestane-3β,6β-diol) inhibited the S phase and stimulated the G0/G1 or G2/M phases. These oxysterols promoted apoptosis, determined with Annexin V and propidium iodide assays. These results showed that different oxysterols have cytotoxic effects depending on the cell line. The findings suggest a potential pharmacological utility of cytotoxic oxysterols. •Several cholesterol oxides were evaluated for their capacity to induce cell death.•Short-term cytotoxicity of oxysterols varied with their type and concentration.•Short-term cytotoxicity of oxysterols varied with the cell lineage.•Cytotoxic oxysterols induced apoptosis in human breast cancer and mouse melanoma.•They also inhibited the S phase and stimulated either the G0/G1 or the G2/M phase.