Searching for the role of membrane sphingolipids in selectivity of antitumor ether lipid-edelfosine.
Edelfosine is a synthetic antitumor lipid of high selectivity. Its activity on membrane level inspired the investigations on edelfosine-lipid interactions to verify, which of the membrane components may be responsible for the selectivity of this drug. Because of overexpression of gangliosides in tumor progression and the ability of edelfosine to insert into membrane rafts, we have chosen two sphingolipids, i.e. sphingomyelin and ganglioside to investigate in mixtures with edelfosine. It was found that edelfosine shows strong affinity to ganglioside in contrast to sphingomyelin. Differences in the interactions of edelfosine with sphingolipids were analyzed from the point of view of the structure and shape of the interacting molecules. The comparison of the results with those previously reported for edelfosine mixed with other membrane components, allowed us to suggest that gangliosides may be considered as target molecules attracting edelfosine to tumor cells.
Hac-Wydro
Katarzyna
K
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland. hac@chemia.uj.edu.pl
Dynarowicz-Łatka
Patrycja
P
D000388:Air; D000970:Antineoplastic Agents / Q000737:chemistry*; D005732:Gangliosides / Q000737:chemistry*; D008567:Membranes, Artificial; D015394:Molecular Structure; D010742:Phospholipid Ethers / Q000737:chemistry*; D013109:Sphingomyelins / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D005732:Gangliosides; D008567:Membranes, Artificial; D010742:Phospholipid Ethers; D013109:Sphingomyelins; D014867:Water; C026659:edelfosine