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.

• Authors: S E Wright, J C White
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 863 Issue 2 Pg. 297-304 (Dec 16 1986) ISSN: 0006-3002 [Print] Netherlands
• PMID: 3024721 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic N-Oxides
• Lipid Bilayers
• Liposomes
• Membrane Lipids
• Spin Labels
• 1,2-Dipalmitoylphosphatidylcholine
• 12-doxylstearic acid
• 5-doxylstearic acid
• Etoposide
• Teniposide
• Cholesterol
• Podophyllotoxin
• Dimyristoylphosphatidylcholine

Topics

• 1,2-Dipalmitoylphosphatidylcholine
• Animals
• Carcinoma, Ehrlich Tumor (ultrastructure)
• Cell Line
• Cell Membrane (drug effects)
• Cholesterol (pharmacology)
• Cyclic N-Oxides
• Dimyristoylphosphatidylcholine
• Electron Spin Resonance Spectroscopy
• Etoposide (pharmacology)
• Humans
• Leukemia (pathology)
• Lipid Bilayers
• Liposomes
• Male
• Membrane Lipids
• Mice
• Podophyllotoxin (analogs & derivatives)
• Spin Labels
• Teniposide (pharmacology)