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

Abstract

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.

• 4 nitroquinoline 1-oxide
• chemoprevention
• grape juice
• oral cancer

Acknowledgements

G.P.P.J., F.A.P.R., C.F.G.M. performed the experimental design and data interpretation. A.P.B.G., C.T.F.O. and D.A.R. performed data interpretation, and writing the manuscript. D.A.R. performed the statistical analysis of this study.