Anti-tumor activity of grape juice concentrate in the rat tongue two-stage initiation-promotion protocol induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the anti-tumor activity of grape juice concentrate following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO). A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received grape juice concentrate at 1% dose by gavage for eight consecutive weeks; Group 3 - received 4NQO for 8 weeks at 20 ppm dose in drinking water daily; Group 4 - received 4NQO at 20 ppm dose during 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage for first 4 weeks after 4-NQO administration; Group 5 - received 4NQO at 20 ppm dose for 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage between the 5th and 8th weeks daily. Histopathological analysis revealed a decrease in hyperplasic and dysplastic lesions in Group 4. Groups 4 and 5 showed decreased COX-2 and TNF-alpha and eNOS gene expression. Grape juice concentrate also increased SOD Cu/Zn and catalase expression. However, Ki-67 immunoexpression was reduced at the promotion step of oral carcinogenesis (G5). Taken together, our results demonstrate that grape juice concentrate modulates rat tongue carcinogenesis as a result of anti-inflammatory activity, antioxidant activity and down-regulation of oral cells proliferation.