Abstract
Abstract Esophageal squamous cell carcinoma (SCC) is the third most common gastrointestinal malignancy and the sixth most frequent cause of cancer death in the world. Nitrosamine carcinogens in tobacco smoke, in the diet, and those produced in the acidic conditions of the stomach, appear to be important causative agents of esophageal SCC. Among these is N-Nitrosomethylbenzylamine (NMBA), present in the diet in China, and likely the most potent nitrosamine carcinogen for the rat esophagus. Our laboratory has used the NMBA-induced esophageal cancer model in rats to identify putative chemopreventive agents, including natural food products, to prevent this disease. Dietary freeze-dried strawberries were found to significantly inhibit tumor development in the rat esophagus by inhibiting the metabolism of NMBA to DNA damaging species and by reducing the growth rate of premalignant cells. Based on these observations, we conducted a Phase I trial in China to investigate the effects of freeze-dried strawberries in a cohort of adult individuals with esophageal dysplastic lesions in a high-risk area for esophageal cancer. In this study, 60 grams of freeze-dried strawberries were given to participants who have been identified by endoscopy to have dysplastic lesions, every day for six months. Biopsy specimens were obtained by endoscopy before and after strawberry treatment. Overall, 36 patients (94.7%) have successfully completed the study, including proper completion of the pre- and post-esophageal endoscopy and biopsy, and the dietary strawberry diary. Twenty patients are females and fifteen patients are males. The average of age is 54.6 ± 1.28. Among 36 patients, 31 patients were diagnosed with mild dysplasia (86.11%) and 5 patients were diagnosed with moderate dysplasia (13.89%). After 6-month strawberry treatment, in patients with mild dysplasia, there was no change in 4 patients, decrease in 26 patients (P < 0.0001) and an increase in 1 patient in histological grade. In patients with moderate dysplasia, there was no change in 2 patients and a decrease in 3 patients in histological grade. Strawberries reduced protein expression levels of inducible nitric oxide synthase (iNOS; 77.3% reduction, P = 0.03), cyclooxygenase-2 (COX-2; 47.3% reduction, P = 0.11), phospho-NFκB-p65 (63.1% reduction, P = 0.23) and phospho-S6 (87.9% reduction, P = 0.02). In addition, we evaluated the effects of strawberries on cell proliferation rate by Ki-67 staining. Strawberries significantly inhibited Ki-67 labeling index by 37.9% (P = 0.023). Our results suggest that strawberries may be a useful alternative to chemopreventive drugs for the prevention of human esophageal cancer. (Supported by California Strawberry Commissions) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-465. doi:10.1158/1538-7445.AM2011-LB-465
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