Suppression of the Inflammatory Cascade is Implicated in Resveratrol Chemoprevention of Experimental Hepatocarcinogenesis
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Resveratrol, present in grapes and red wine, has been found to prevent diethylnitrosamine (DENA)-initiated rat liver tumorigenesis, though the chemopreventive mechanisms are not completely elucidated. The current study was designed to explore whether the antiinflammatory properties of resveratrol play a role in its antihepatocarcinogenic action.
Liver samples were harvested from a 20-week chemopreventive study in which resveratrol (50, 100 and 300 mg/kg) was shown to inhibit DENA-induced hepatocyte nodules in Sprague-Dawley rats in a dose-responsive manner. Hepatic preneoplastic and inflammatory markers, namely heat shock protein (HSP70), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), were studied using immunohistochemical as well as Western blot techniques.
Resveratrol dose-dependently suppressed DENA-induced increased expressions of hepatic HSP70 and COX-2. Resveratrol also attenuated the DENA-mediated translocation of NF-κB p65 from the cytosol to the nucleus with stabilization of inhibitory κB.
The present findings indicate that resveratrol exerts chemoprevention of hepatocarcinogenesis possibly through antiinflammatory effects during DENA-evoked rat liver carcinogenesis by suppressing elevated levels of HSP70, COX-2 as well as NF-κB. These beneficial effects combined with an excellent safety profile encourage the development of resveratrol for chemoprevention and intervention of human HCC that remains a devastating disease.
KEY WORDSchemoprevention hepatocarcinogenesis inflammation NF-κB resveratrol
hepatitis B virus
hepatitis C virus
heat shock protein 70
inhibitor of κB
inducible nitric oxide synthase
nuclear factor-kappa B
reactive oxygen species
This work was supported by a Research Incentive Grant from Ohio Board of Regents, State of Ohio. The authors sincerely thank Cornelis Van der Schyf, D.Sc., DTE, for his constant support and encouragement, Howard P. Glauert, Ph.D., for helpful discussions, and Werner J. Geldenhuys, Ph.D., for technical assistance with the structure of resveratrol.
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