Pharmaceutical Research

, Volume 27, Issue 6, pp 1080–1091 | Cite as

Suppression of the Inflammatory Cascade is Implicated in Resveratrol Chemoprevention of Experimental Hepatocarcinogenesis

  • Anupam BishayeeEmail author
  • Abhijeet Waghray
  • Kendra F. Barnes
  • Thomas Mbimba
  • Deepak Bhatia
  • Malay Chatterjee
  • Altaf S. Darvesh
Research Paper



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.


chemoprevention hepatocarcinogenesis inflammation NF-κB resveratrol 







hepatitis B virus


hepatocellular carcinoma


hepatitis C virus


horseradish peroxidase


heat shock protein 70


inhibitor of κB


inducible nitric oxide synthase


nuclear factor-kappa B




phosphate-buffered saline




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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anupam Bishayee
    • 1
    Email author
  • Abhijeet Waghray
    • 1
  • Kendra F. Barnes
    • 1
  • Thomas Mbimba
    • 1
  • Deepak Bhatia
    • 1
  • Malay Chatterjee
    • 2
  • Altaf S. Darvesh
    • 1
  1. 1.Department of Pharmaceutical Sciences Cancer Therapeutics and Chemoprevention Emphasis GroupNortheastern Ohio Universities Colleges of Medicine and PharmacyRootstownUSA
  2. 2.Department of Pharmaceutical Technology, Division of BiochemistryJadavpur UniversityKolkataIndia

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