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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

ABSTRACT

Purpose

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.

Methods

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.

Results

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.

Conclusion

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 WORDS

chemoprevention hepatocarcinogenesis inflammation NF-κB resveratrol 

ABBREVIATIONS

COX-2

cyclooxygenase-2

DENA

diethylnitrosamine

HBV

hepatitis B virus

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

HRP

horseradish peroxidase

HSP70

heat shock protein 70

IκB

inhibitor of κB

iNOS

inducible nitric oxide synthase

NF-κB

nuclear factor-kappa B

PB

phenobarbital

PBS

phosphate-buffered saline

PGs

prostaglandins

ROS

reactive oxygen species

Notes

ACKNOWLEDGMENTS

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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