Laura Martin, Maria and Barcelo-Coblijn, Gwendolyn and de Almeida, Rodrigo F. M. and Antonia Noguera-Salva, Maria and Teres, Silvia and Higuera, Monica and Liebisch, Gerhard and Schmitz, Gerd and Busquets, Xavier and Escriba, Pablo V. (2013) The role of membrane fatty acid remodeling in the antitumor mechanism of action of 2-hydroxyoleic acid. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1828 (5). pp. 1405-1413. ISSN 0005-2736, 0006-3002
Full text not available from this repository. (Request a copy)Abstract
The synthetic fatty acid 2-hydroxyoleic acid (20HOA) is a potent antitumor drug that we rationally designed to regulate the membrane lipid composition and structure. The lipid modifications caused by 20HOA treatments induce important signaling changes that end up with cell death (Teres et al., 2012 [1]). One of these regulatory effects is restoration of sphingomyelin levels, which are markedly lower in cancer cells compared to normal cells (Barcelo-Coblijn et al., 2011 [2]). In this study, we report another important regulatory effect of 20HOA on cancer cell membrane composition: a large increase in 20HOA levels, accounting for similar to 15% of the fatty acids present in membrane phospholipids, in human glioma (SF767 and U118) and lung cancer (A549) cells. Concomitantly, we observed marked reductions in oleic acid levels and inhibition of stearoyl-CoA desaturase. The impact of these changes on the biophysical properties of the lipid bilayer was evaluated in liposomes reconstituted from cancer cell membrane lipid extracts. Thus, 20HOA increased the packing of ordered domains and decreased the global order of the membrane. The present results further support and extend the knowledge about the mechanism of action for 20HOA, based on the regulation of the membrane lipid composition and structure and subsequent modulation of membrane protein-associated signaling. (C) 2013 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FLUORESCENCE LIFETIME SPECTROSCOPY; TIME-RESOLVED FLUORESCENCE; COA DESATURASE; LIPID DOMAINS; ANTICANCER ACTIVITY; CANCER-CELLS; RAFTS; PROTEIN; INHIBITION; MINERVAL; Sphingolipid; Membrane lipid therapy; Cancer; Stearoyl-CoA desaturase |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Apr 2020 06:21 |
| Last Modified: | 16 Apr 2020 06:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16778 |
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