5-doxylstearate and Leukemia

The effect of the anticancer agent VM-26 on acyl chain order of cellular and model membranes was examined by electron spin resonance techniques. The order parameter for the paramagnetic probe 5-doxyl stearate was increased when VM-26 was incorporated into the bilayer of fluid-phase dimyristoylphosphatidylcholine (DMPC) or gel-phase dipalmitoylphosphatidylcholine (DPPC) liposomes at concentrations up to 4.8 mol%. The ordering effect of VM-26 in DMPC was greater than that of cholesterol on an equimolar basis. The less cytotoxic congener of VM-26, VP-16, was only one-third as active as VM-26 in its ordering effects on DMPC. Higher order parameters for 5-doxyl stearate were also noted in asolectin liposomes, Ehrlich ascites tumor cells, and CCRF-CEM cells treated with VM-26. We conclude that VM-26 has significant membrane associated activity in addition to its previously recognized nuclear effects.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Carcinoma, Ehrlich Tumor; Cell Line; Cell Membrane; Cholesterol; Cyclic N-Oxides; Dimyristoylphosphatidylcholine; Electron Spin Resonance Spectroscopy; Etoposide; Humans; Leukemia; Lipid Bilayers; Liposomes; Male; Membrane Lipids; Mice; Podophyllotoxin; Spin Labels; Teniposide