The role of membrane fatty acid remodeling in the antitumor mechanism of action of 2-hydroxyoleic acid

Biochim Biophys Acta. 2013 May;1828(5):1405-13. doi: 10.1016/j.bbamem.2013.01.013. Epub 2013 Jan 27.


The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) is a potent antitumor drug that we rationally designed to regulate the membrane lipid composition and structure. The lipid modifications caused by 2OHOA treatments induce important signaling changes that end up with cell death (Terés 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 (Barceló-Coblijn et al., 2011 [2]). In this study, we report another important regulatory effect of 2OHOA on cancer cell membrane composition: a large increase in 2OHOA levels, accounting for ~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, 2OHOA 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 2OHOA, based on the regulation of the membrane lipid composition and structure and subsequent modulation of membrane protein-associated signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Biophysical Phenomena
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / chemistry*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chromatography, Thin Layer
  • Fatty Acids / chemistry*
  • Fatty Acids / metabolism
  • Humans
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Mass Spectrometry
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism
  • Neoplasms / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Oleic Acids / chemistry*
  • Oleic Acids / metabolism
  • Oleic Acids / pharmacology
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / metabolism
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / metabolism
  • Phospholipids / chemistry
  • Phospholipids / metabolism
  • Stearoyl-CoA Desaturase / antagonists & inhibitors
  • Stearoyl-CoA Desaturase / metabolism
  • Time Factors
  • Triglycerides / chemistry
  • Triglycerides / metabolism


  • 2-hydroxyoleic acid
  • Antineoplastic Agents
  • Fatty Acids
  • Lipid Bilayers
  • Membrane Lipids
  • Oleic Acids
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Phospholipids
  • Triglycerides
  • phosphatidylethanolamine
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase