Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IκB kinase

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Creator
  • Holmes-McNary, Minnie
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Baldwin, Albert
Abstract
  • trans-Resveratrol (Res), a phytoalexin found at high levels in grapes and in grape products such as red wine, has been shown to have anti-inflammatory and antioncogenic properties. Because the transcription factor nuclear factor kappaB (NF-kappaB) is involved in inflammatory diseases and oncogenesis, we tested whether Res could modulate NF-kappaB activity. Res was shown to be a potent inhibitor of both NF-kappaB activation and NF-kappaB-dependent gene expression through its ability to inhibit IkappaB kinase activity, the key regulator in NF-kappaB activation, likely by inhibiting an upstream signaling component. In addition, Res blocked the expression of mRNA-encoding monocyte chemoattractant protein-1, a NF-kappaB-regulated gene. Relative to cancer chemopreventive properties, Res induced apoptosis in fibroblasts after the induced expression of oncogenic H-Ras. Thus, Res is likely to function by inhibiting inflammatory and oncogenic diseases, at least in part, through the inhibition of NF-kappaB activation by blocking IkappaB kinase activity. These data may also explain aspects of the so-called "French paradox" that is associated with reduced mortality from coronary heart disease and certain cancers and provide a molecular rationale for the role of a potent chemopreventive compound in blocking the initiation of inflammation and oncogenesis.
Date of publication
DOI
Identifier
  • 2-s2.0-0034234254
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Cancer Research
Journal volume
  • 60
Journal issue
  • 13
Page start
  • 3477
Page end
  • 3483
Language
  • English
Version
  • Postprint
ISSN
  • 1538-7445

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