Distribution of tumor promoters in lipid membranes and changes in membrane structure

The interaction of tumor promoters differing in molecular structure, namely, 12-O-tetradecanoylphorbol 13-acetate (TPA) and teleocidin, with dipalmitoylphosphatidylcholine (DPPC) vesicles was studied. Investigation by Fourier transform infrared spectroscopy clarified the differences between the tumor promoters in the mode of interaction with lipid bilayer membranes. The temperature dependence of the bandwidth of the C-H or C = O stretching absorption of lipid molecules in the presence of tumor promoters relative to that in pure DPPC vesicles indicated that TPA is incorporated into the hydrophobic core of the lipid bilayer membrane whilst teleocidin binds predominantly to the membrane surface. However, both tumor promoters tend to restrict the motion of lipid molecules in membranes. The same conclusion was derived from measurements of steady-state fluorescence polarization, which showed that tumor promoters decreased the membrane fluidity. On the other hand, carboxyfluorescein (CF) leakage from vesicles was enhanced by the addition of TPA below the phase-transition temperature, whereas the effect of teleocidin on steady-state CF leakage was not as significant. It is considered that the difference in the profile of the TPA-induced increase in CF leakage compared to that of teleocidin might be ascribable to a different binding site for each tumor promoter in the membranes.