title: Membrane ordering effects of the anticancer agent VM-26.
abstract: 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.
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000648:ultrastructure; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects*; D002784:Cholesterol / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004134:Dimyristoylphosphatidylcholine; D004578:Electron Spin Resonance Spectroscopy; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008051:Lipid Bilayers; D008081:Liposomes; D008297:Male; D008563:Membrane Lipids; D051379:Mice; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013113:Spin Labels; D013713:Teniposide / Q000494:pharmacology*
chemical_list: D003497:Cyclic N-Oxides; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D013113:Spin Labels; D015060:1,2-Dipalmitoylphosphatidylcholine; C037404:12-doxylstearic acid; C005072:5-doxylstearic acid; D005047:Etoposide; D013713:Teniposide; D002784:Cholesterol; D011034:Podophyllotoxin; D004134:Dimyristoylphosphatidylcholine