Zusammenfassung
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 ...
Zusammenfassung
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.
Altmetric