Prominent chemopreventive and chemoenhancing effects for resveratrol: unraveling molecular targets and the role of C-reactive protein.

Background: Resveratrol (RSVL) claims health benefits that pertain to the consumption of red wine/grapes. We currently evaluated the chemopreventive effects of RSVL, as well as its possible chemoenhancing effects when given with cisplatin (CP), in the Ehrlich ascites carcinoma (EAC) solid tumor model. Further, we monitored concomitant changes in serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), leukocytic count (LC) and lipid peroxidation (measured as malondialdehyde, MDA).

Results: EAC-bearing mice exhibited a markedly elevated LC (2 fold), CRP (11 fold) and MDA levels (2.7 fold). RSVL (20 or 40 mg/kg) elicited significant, dose-dependent reductions in tumor size (58 and 78%, respectively), as well as in LC (normalized), CRP (down to 2 fold), TNF-alpha (down to near control levels) and MDA levels (normalized). The chemopreventive effects for CP (55% reduction in cell growth) was significantly lower than that of RSVL (40 mg/kg, 79% inhibition). Interestingly, coadministration of RSVL (20 mg/kg) markedly enhanced the chemoprevention of CP. Correlation studies revealed a high degree of positive association between tumor growth and CRP (r = 0.89) and leukocytosis (r = 0.86), thus attesting to a diagnostic/prognostic role for CRP in this solid tumor.

Conclusion: RSVL elicited remarkable cytotoxicity on its own and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels. RSVL acts prominently by reducing inflammatory cytokines, leukocytosis and oxidative stress.