Characterization of the grape seeds extract effect against chemically -induced liver cancer: In vivo and in vitro analyses

The present study provides evidence that the GSE’s anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.What is it about?The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and acetylaminofluorene. Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-treated rats by approximately 4 & 10 fold deductions, respectively. GSE’s effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p- phosphorylated tumor necrosis factor receptor expressions in liver.Why is it important?The data presented here show that GSE dramatically inhibited FAH formation in livers of DEN-treated rats. GSE’s effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of HDAC activity and inflammation makers, such as COX-2, iNOS, NF-κB-p65 and p-TNFR1 expressions. Those effects are schematically depicted in figure , which incorporates our data into a model showing a possible mechanism of the anti-cancer protective effect of GSE by promoting apoptosis, inhibiting cell proliferation and blocking inflammation in hepatocarcinomas.