Combination of the anti-tumour cell ether lipid edelfosine with sterols abolishes haemolytic side effects of the drug

Journal of Chemical Biology

Félix M. Goñi¹  Faustino Mollinedo²  Jon V. Busto¹  Esther del Canto-Jañez²  Alicia Alonso¹ 

[1] Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain;Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain

关键词: Edelfosine;    Ether lipid;    Sterols;    Antitumour drugs;    Lipid molecular geometry;    Surface pressure;   

DOI  :  10.1007/s12154-008-0009-z

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is an anti-tumour cell ether lipid with surface-active properties. Pure edelfosine can be dispersed in aqueous media in the form of micelles. One important, negative side effect of edelfosine is that it is highly haemolytic. In this paper, we show that edelfosine can be co-dispersed in water with certain lipids (particularly cholesterol, campesterol or β-sitosterol) so that it gives rise to liposomes. Surface pressure measurements demonstrate that edelfosine is slowly released from these liposomes. In liposomal form, edelfosine remains apoptogenic for a variety of leukemia cell lines, while its haemolytic effect is abolished. The phenomenon is explained on the basis of the complementarity of the molecular geometries of sterols and edelfosine.

【 授权许可】

Unknown