Oxysterols selectively promote short-term apoptosis in tumor cell lines

Author(s)

Levy, Debora ^[1] ; de Melo, Thatiana Correa ^[1] ; Ohira, Bianca Yumi ^[2] ; Fidelis, Maira Luisa ^[2] ; Ruiz, Jorge L. M. ^[3] ; Rodrigues, Alessandro ^[2] ; Bydlowski, Sergio P. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Genet & Mol Hematol LIM31, Dept Hematol, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Quim, Diadema, SP - Brazil

^[3] Fed Univ Latin Amer Integrat UNILA, Life & Nat Sci Inst, Foz Do Iguacu, PR - Brazil

^[4] CNPq, Inst Nacl Ciencia & Tecnol Med Regenerat INCT Reg, Brasilia, DF - Brazil

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 505, n. 4, p. 1043-1049, NOV 10 2018.
• Web of Science Citations: 4

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 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-3 beta-5 alpha-6 beta-triol, and 5 alpha-cholestane-3 beta,6 beta-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. (C) 2018 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 16/21676-0 - Enantioselective haloamination reactions aiming the synthesis of aminodiols
• Grantee: Alessandro Rodrigues
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/10073-5 - Organocatalysis: design, synthesis and applications in stereoselective organic reactions
• Grantee: Alessandro Rodrigues
• Support Opportunities: Regular Research Grants