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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
15-POS
Board 15
Edelfosine Shows Affinity for Cholesterol and Disorganizes Liquid Ordered Structures
Juan Gomez-Fernandez
, Pablo Hernández-Valera, Monika Schneider, Victoria Gomez-Murcia,
Ana M. DeGodos, Alejandro Torrecillas, Senena Corbalan-Garcia.
University of Murcia, Murcia, Spain.
Edelfosine is an alkl-lysophospholipid with antineoplastic and immunomodulating effects. We
compare here the effect of edelfosine on the organization, at different temperatures, of liquid
ordered membrane-like structures, with four other asymmetric phospholipids, PAF, PAPC,
lysoPAF and lysoPC. When a POPC/SM/cholesterol (1:1:1 mole ratio) ternary mixture was
studied by DSC no phase transition was detected, but the addition of 20 mol % edelfosine to
produced a phase transition Lβ to Lα. This new transition should be attributed to the association
of edelfosine to cholesterol capable of neutralizing its effect. Such a transition was not produced
by the addition of the other four asymmetric phospholipids. Results from SAXD showed that
edelfosine, PAF and PAPC at 5 and 15°C produced spacings that suggest lamellar crystalline
structure, while at 45°C results indicated a bilayer structure in fluid state. In contrast, lysoPC
produces a crystalline structure at 5 and 15°C, while at 45°C was in a bilayer in fluid state.
Furthermore, the spacing of the sample with lysoPAF at 5°C indicates that it has two phases,
probably both of lamellar type. At 15°C the pattern displays a spacing indicating that one of the
two phases disappeared, while at 45°C two spacings indicate that the lamellar phase that remains
is a bilayer in fluid state. 31P-NMR showed that edelfosine forms bilayers when combined with
just cholesterol, being more capable of doing so than the other compounds studied. These
bilayers were characterized by microscopy. The results obtained in this study support the theory
that the antitumor drug edelfosine acts through reorganization and modification of lipid rafts in
liquid ordered state (Lo) and therefore supports that these domains are a promising therapeutic
target against cancer.