The cancer chemopreventive agent resveratrol is incorporated into model membranes and inhibits protein kinase C alpha activity

Resveratrol is a phytoalexin found in grapes and other foods that cancer ch emopreventive and other biological activities have been attributed recently . We report that resveratrol is able to incorporate itself into model membr anes in a location that is inaccessible to the fluorescence quencher, acryl amide. Differential scanning calorimetry revealed that resveratrol consider ably affected the gel to liquid-crystalline phase transition of multilamell ar vesicles made of phosphatidylcholine/phosphatidylserine and increased th e temperature at which the fluid lamellar to H-II inverted hexagonal transi tion took place in multilamellar vesicles made of 1,2 -dielaidoyl-sn-phosph atidylethanolamine, Such a transition totally disappeared at 2.5 mM of resv eratrol (resveratrol/lipid molar ratio of 2:1). This effect on 1,2-dielaido yl-sn-phosphatidylethanolamine polymorphism was confirmed through P-31-NMR, which showed that an isotropic peak appeared at high temperature instead o f the H-II-characteristic peak of 42 mM of resveratrol (resveratrol/lipid m olar ratio of 1.5:1). Finally, resveratrol inhibited PKC alpha when activat ed by phosphatidylcholine/phosphatidylserine vesicles with an IC50 of 30 mu M, whereas when the enzyme was activated by Triton X-100 micelles the IC50 was 300 mu M. These results indicate that the inhibition of PKC alpha by r esveratrol can be mediated, at least partially, by membrane effects exerted near the lipid-water interface. (C) 1999 Academic Press.