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

• DOI: 10.1007/s11095-010-0144-4
• Publication Date: 2010-04-19T16:06:03Z
• Authors: Anupam Bishayee; Abhijeet Waghray; Kendra F. Barnes; Thomas Mbimba; Deepak Bhatia; Malay Chatterjee; Altaf S. Darvesh
• Keywords: Inflammation; 0301 basic medicine; Liver Neoplasms; NF-kappa B; Chemoprevention; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Liver; Cyclooxygenase 2; Resveratrol; Stilbenes; Animals; Anticarcinogenic Agents; Humans; Diethylnitrosamine; Female; HSP70 Heat-Shock Proteins

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-kappaB (NF-kappaB), 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-kappaB p65 from the cytosol to the nucleus with stabilization of inhibitory kappaB.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-kappaB. 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.