The relationship between the concentration of ganglioside GM1 and antitumor activity of edelfosine—The Langmuir monolayer study

One of the characteristic features of tumor membranes is altered concentration of gangliosides level and their over-expression in tumor progression. This fact should be considered when the mechanism of activity and selectivity of edelfosine (ED) – a membrane-active anticancer drug – is investigated. Strong affinity of this drug to ganglioside GM1, found in binary mixed monolayers, encouraged us for a deeper investigations on more complex model systems. In this work we have studied the influence of edelfosine on the interactions between molecules in model sphingomyelin/cholesterol monolayer, mimicking a tumor membrane, containing ganglioside in increasing proportion that is characteristic of cancer progression. It was found that edelfosine in very low concentration (1%) practically does not influence on model membrane system, independently of the proportion of ganglioside. On the other hand, at the increased ED concentration (10%), the interactions between the lipids in the mixed system become progressively stronger upon the increase of ganglioside concentration as compared to those in the model tumor membrane. The results of our investigations show that the affinity of edelfosine towards tumor cells may be correlated with over-expression of gangliosides in cancer cells.