Introduction In the US, prognosis for oral cancer is poor with low 5- and 10-year survival rates. These rates have remained relatively constant over the last three decades, with 20%-30% of oral cancer survivors experiencing a recurrence within two years. Since current treatments are relatively ineffective at inhibiting recurrence, it is important that novel preventive strategies be developed. The hamster cheek pouch (HCP) model has shown that biochemical, molecular and histological changes between humans and hamsters are maintained during oral carcinogenesis. We have used the HCP to demonstrate the chemopreventive efficacy of black raspberries and translated these findings into human clinical trials. We have now focused our efforts on another food-based chemopreventive agent, strawberries, and have recently demonstrated that dietary lyophilized strawberries (LS) significantly inhibited tumor formation in Complete Chemoprevention (CC) and Post-initiation (PI) assays in the HCP model. Epidemiologic and chemoprevention studies have demonstrated that selenium (Se) can decrease the risk and incidence of some human cancers through pathways such as apoptosis, detoxification, and inhibition of proliferation. The current study illustrates ongoing pre-clinical efforts aimed at evaluating the chemopreventive efficacy of selinium (Se)-enriched lyophilized strawberries (LS+Se). Previous studies have shown that elemental and organoselenium compounds inhibited tongue carcinogenesis in animal models. Therefore, we hypothesize that the combinatorial administration of LS+Se will inhibit oral tumorigenesis to a greater extent than LS-alone.
Methods Strawberries with bioincorporated selenium (0.5 and 1.0 ppm) were prepared by spraying sodium selenate solution three times on the leaves of the plants just before and during blossom. The HCP model was used to evaluate the ability of LS and LS+Se to inhibit 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral tumors. LS and LS+Se were incorporated into AIN-76A pellets 10% (w/w) and given to hamsters before, during, and after carcinogen treatment (CC). At 12 weeks, lesions in each cheek pouch were enumerated. HCP were excised and stored appropriately for subsequent studies.
Results Poisson regression demonstrated that 10% LS and 10% LS+Se [0.5 ppm] significantly inhibited tumor formation by 43% and 59%, respectively, over DMBA-only treated controls. Using logistic regression with the dependent variable being presence or absence of tumors, it was found that LS+Se were 3x as likely to have no tumors (95% CI: 1.31-8.33) as DMBA-only treated HCP. LS-alone was 2.2x as likely to have no tumors, but this difference was not significantly different than DMBA-only treated groups. The presence of leukoplakias was significantly increased with LS+Se and LS, suggesting that progression from premaligant lesions to overt tumors was inhibited by LS and to an even greater effect with LS+Se.
Discussion and Conclusion While trends were evident for the combinatorial effects of LS+Se, the current study could not demonstrate statistical significances between the chemopreventive role of LS-alone versus LS+Se. Overall, these experiments provide strong preclinical evidence that the strawberries and strawberries with selenium can prevent or delay the development of oral cavity cancer.
Support: NIH/NCI R03CA128043
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B96.
- American Association for Cancer Research