Studies on the interactions of anticancer drug - Minerval - with membrane lipids in binary and ternary Langmuir monolayers

摘要

2-Hydroxyoleic acid (2OHOA, Minerval), a derivative of oleic acid, is the lipid used in Membrane Lipid Therapy. This compound is of confirmed anticancer effect, however its exact mechanism of action has not been fully elucidated. In this work the interactions of 2OHOA with cholesterol, sphingomyelin and phosphatidylcholine in Langmuir films were investigated. Moreover, the influence of this drug on SM/Chol and POPC/Chol films was studied. The collected results evidenced that 2OHOA substantially increases fluidity of lipid monolayers and modifies membrane organization, however, its influence depends on drug concentration and membrane properties. It was found that the condensation of model membrane is a critical factor determining the effect of 2OHOA. Moreover, the drug molecules added into SM/Chol film treated as model raft system drastically decrease molecular packing, weaken the interactions between raft components, destabilize the system and alter its morphology. This allows one to suggest that alterations made directly in membrane and microdomains architecture can be treated as one of the areas of Minerval activity.