Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the I kappa B kinase

trans-Resveratrol (Res), a phytoalexin found at high levels in grapes and i n grape products such as red wine, has been shown to have antiinflammatory and antioncogenic properties. Because the transcription factor nuclear fact or kappa B (NF-kappa B) is involved in inflammatory diseases and oncogenesi s, we tested whether Res could modulate NF-kappa B activity. Res was shown to be a potent inhibitor of both NF-kappa B activation and NF-kappa B-depen dent gene expression through its ability to inhibit I kappa B kinase activi ty, the key regulator in NF-kappa B activation, likely by inhibiting an ups tream signaling component. In addition, Res blocked the expression of mRNA- encoding monocyte chemoattractant protein-1, a NF-kappa B-regulated gene, R elative to cancer chemopreventive properties, Res induced apoptosis in fibr oblasts after the induced expression of oncogenic H-Ras, Thus, Res is likel y to function by inhibiting inflammatory and oncogenic diseases, at least i n part, through the inhibition of NF-kappa B activation by blocking I kappa B kinase activity, These data may also explain aspects of the so-called "F rench paradox" that is associated with reduced mortality from coronary hear t disease and certain cancers and provide a molecular rationale for the rol e of a potent chemopreventive compound in blocking the initiation of inflam mation and oncogenesis.