Effects of antineoplastic ether lipids on model and biological membranes.

Differential scanning calorimetry and electron spin resonance were utilized to measure the effects of di-ether glycerophospholipid analogs (EL) on the physical properties of model membranes and on the membrane fluidity of HL60 leukemic cells. 1-Octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) and 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine (ET-16S-OEt) lower the transition temperature of dimyristoylphosphatidylcholine vesicles in a range of concentrations between 0.5 and 15 mol %. Studies conducted on the interaction of EL with a wide spectrum of different phospholipids, namely dipalmitoylphosphatidylcholine, 1-hexadecyl-2-palmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and dielaidoylphosphatidylethanolamine confirmed the ability of EL to effect the physical properties of model membranes. Changes in calorimetric enthalpy were observed only with phosphatidylethanolamine-containing phospholipids. ET-18-OMe and ET-16S-OEt increased the membrane fluidity of HL60 leukemic cells labeled with the fatty acid spin label probe 5-nitroxystearate. These data demonstrate the ability of EL to partition into phospholipidic domains and to change their physical properties. Furthermore, they affect the membrane fluidity of whole cells. These effects indicate an interaction between EL and the plasma membrane which may be of importance in determining the cytotoxic activity against tumor cells exerted by EL.