Chemoprevention of oral cancer by lyophilized strawberries.

Background/Aim: Oral cancer represents approximately 2.5% of all cancers in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. Materials and Methods: HCPs were painted three times a week for six weeks with 0.2% 7,12- dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors was determined. Results: A significant difference (p<0.01-0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. Conclusion: These experiments support previous studies in HCP that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer. Oral cancer is the sixth most common type of cancer in the world (1-3) and represents approximately 2.5% of all cancer in the United States (4). For all stages, one-year survival rate is approximately 84%, with five- and 10-year survival rates of 62% and 51%, respectively, which have slowly declined over the past three decades (4). The overall survival rate is one of the lowest among the major sites of cancer and may be attributed to cancer tending to be diagnosed at advanced stages and a general lack of knowledge in the general population concerning the risks and signs of oral cancer (5). In addition, recurrence is a problem since 20% of patients may exhibit locoregional recurrence within two years' post- surgery and 22-42% of oral cancer patients will present with a second primary tumor within 5-8 years (6, 7). Major risk factors for oral cancer in the United States are the use of tobacco and alcoholic beverages, which may account for ~75% of all oral cancer (8, 9, 10). Epidemiological studies have shown a strong correlation between the consumption of fresh fruits and vegetables and a decreased risk for oral cancer (11). In support of these observations, a series of pre-clinical investigations have demonstrated that black raspberries (Rubus occidentalis) prevent development of chemically-induced oral, esophageal, and colon cancer (12, 13, 14) in rodent models and Carlton et al. (15) showed that strawberries (Fragaria × ananassa) inhibit esophageal cancer in rats. Strawberries are of interest due to their ability to be cultivated in most parts of the world and their large content of bioactive components with potential chemopreventive activity, including vitamins A, C, and E; folic acid, calcium, selenium, β-sitosterol, ellagic and ferulic acids; flavonols such as kaempferol and quercetin; and multiple anthocyanins (16). Preliminary evidence that components of strawberries may have chemopreventive potential originates from the findings that strawberry extracts inhibit the proliferation of human cancer cells and induce apoptosis in vitro (17, 18, 19, 20) and inhibit activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) in cultured cells (21). The pharmacological and chemopreventive activity of individual components of various fruits are reviewed by Stoner and Casto (22) and by Seeram (23). Based on literature data and results with black raspberries and strawberries in rodent models of aerodigestive tract cancer, we postulated that dietary administration of strawberries would inhibit the occurrence of malignant oral lesions and modify expression of genes related to the development of oral cancer.