The influence of 2-hydroxyoleic acid – an anticancer drug – on model membranes of different fluidity modulated by the cholesterol content

Abstract

2-Hydroxyoleic acid (2OHOA, Minerval) is a Membrane Lipid Therapy drug with anti-cancer activity. Therapeutic effect of this substance is associated with its incorporation into cell membrane. However, despite its effectiveness in cancer treatment and the lack of the side effects, the molecular mechanism of Minerval action is not fully clarified. In this study the influence of 2OHOA on fluidity, permeability and molecular organization of artificial lipid membranes in the context of its membrane-related anticancer properties was investigated. The experiments were performed for raft-like model, composed of the equimolar mixture of sphingomyelin, palmitoyloleoylphosphatidylcholine and cholesterol, as well as for the systems with lower cholesterol content. As model membranes Langmuir films and liposomes were applied. The obtained findings reveal that the incorporation of 2OHOA into artificial lipid membranes leads to the alterations in the properties of the systems. It was found that 2OHOA provokes the chain-disordering, fluidization and the increase in permeability of the studied systems. Both the results of monolayers and bilayers studies show that the strongest 2OHOA effect is observed for raft like mixture. The latter may indicate that the molecular mechanism of action of this compound is closely related to its interactions with lipid rafts – domains that are responsible for the regulation of various cellular functions.