The Cancer Chemopreventive Agent Resveratrol Is Incorporated into Model Membranes and Inhibits Protein Kinase C α Activity

Resveratrol is a phytoalexin found in grapes and other foods that cancer chemopreventive and other biological activities have been attributed recently. We report that resveratrol is able to incorporate itself into model membranes in a location that is inaccessible to the fluorescence quencher, acrylamide. Differential scanning calorimetry revealed that resveratrol considerably affected the gel to liquid-crystalline phase transition of multilamellar vesicles made of phosphatidylcholine/phosphatidylserine and increased the temperature at which the fluid lamellar to HII inverted hexagonal transition took place in multilamellar vesicles made of 1,2-dielaidoyl-sn-phosphatidylethanolamine. Such a transition totally disappeared at 2.5 mM of resveratrol (resveratrol/lipid molar ratio of 2:1). This effect on 1,2-dielaidoyl-sn-phosphatidylethanolamine polymorphism was confirmed through 31P-NMR, which showed that an isotropic peak appeared at high temperature instead of the HII-characteristic peak of 42 mM of resveratrol (resveratrol/lipid molar ratio of 1.5:1). Finally, resveratrol inhibited PKCα when activated by phosphatidylcholine/phosphatidylserine vesicles with an IC50 of 30 μM, whereas when the enzyme was activated by Triton X-100 micelles the IC50 was 300 μM. These results indicate that the inhibition of PKCα by resveratrol can be mediated, at least partially, by membrane effects exerted near the lipid–water interface.