The anticancer drug adriamycin interacts with the human erythrocyte membrane

Adriamycin is an aminoglycosidic anthracycline antibiotic widely used in th e treatment of cancer. Increasing reports point to the involvement of cell membranes in its mechanism of action. The interaction of adriamycin with hu man erythrocytes was investigated in order to determine the membrane bindin g sites and the resultant structural perturbation. Electron microscopy reve aled that red cells incubated with the therapeutical concentration of the d rug in human plasma changed their discoid shape to both stomatocytes and ec hinocytes. According to the bilayer couple hypothesis, this means that adri amycin was incorporated into either the inner or outer leaflets of the eryt hrocyte membrane. To explain this unusual result, the drug was incubated wi th molecular models. One of them consisted of dimyristoylphosphatidylcholin e (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) multilayers, repres entative of phospholipid classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. X-ray diffraction showed that adri amycin interaction perturbed the polar head and acyl chain regions of both lipids. Fluorescence spectroscopy on another model, consisting of DMPC larg e unilamellar vesicles (LUV), confirmed the X-ray results in that adriamyci n fluidized its hydrophobic moiety. It is concluded that adriamycin incorpo rates into both erythrocyte leaflets affecting its membrane structure.