Abstract LB-185: Inhibitory effects of black raspberry consumption on prostate carcinogenesis in rats.

Abstract

Abstract Black raspberries are being developed to chemoprevent GI tract cancers in humans and they have been shown to prevent breast cancer development in a rat model. Therefore, it is important to determine whether they can also prevent other major human cancers such as prostate cancer. We induced prostate cancer in Wistar HsdCpb:WU rats by treatment with Flutamide (20 mg/kg BW by gavage daily for 20 days), a single SC injection with testosterone propionate (100 mg/kg) on day 21, and single IP injection of N-methyl-N-nitrosourea (MNU; 30 mg/kg) 52-56 hrs later. Two weeks later, rats received two SC Silastic tubing implants (ID 0.078 in; OD 0.125 in.) containing crystalline testosterone tightly packed over 3 cm length. One week later, rats were started on AIN-93M diet (control) or isoenergetic AIN-93M diets containing 5% or 10% lyophilized black raspberry powder (exchanged for starch). The powder was from a single batch of freshly harvested black raspberries (BerriProducts, Corvallis, OR), stored at -20oC until mixed into the diet, and provided fresh to the rats thrice weekly. The treatment did not affect body weight gain or survival (mean 49-52 wks). The study was terminated 58 weeks after MNU and at necropsy prostate complexes and all tumor-like lesions were collected for histology. Prostate cancer incidence was determined by enumerating grossly observed tumors and histopathologic evaluation using step sections. Overall incidence of large prostate tumors, histologically confirmed as adenocarcinomas, was reduced from 16/31 rats in the control group (52%) to 14/30 (46%) and 8/30 (27%) rats in the low and high dose black raspberry groups, resp., which trend was significant (p = 0.049; X2 test). The difference in incidence between control and high dose groups was borderline significant (p = 0.067, 2-sided; p = 0.41, 1-sided Fisher exact test). In subgroups of 4-5 rats, the prostate was collected after 3 weeks of feeding the diets and the concentrations of the black raspberry anthocyanin metabolite protocatechuic acid (PCA) were measured in the lateral prostate using LC-MS/MS. Mean (± SD) prostatic concentrations of PCA (ng/g wet tissue) were 0.5 ± 0.0 (detection limit), 3.64 ± 1.35 (p<0.05), and 4.61 ± 1.92 (p<0.01) in the control, low, and high dose groups, resp. (overall p = 0.009; Kruskall-Wallis test). Preliminary results of in vitro studies with black raspberry constituents indicated that ellagic acid, which is more stable than anthocyanins, reduced growth of human LAPC-4 prostate cancer cells by ≥ 25% at concentrations of 10 μg/ml and higher. These results indicate that black raspberry consumption (1) can inhibit prostate cancer induction in rats, (2) results in significant amounts of an anthocyanin metabolite in the rat prostate, and (3) ellagic acid, a major bioactive agents in black raspberries, can inhibit in vitro growth of human prostate cancer cells. (Supported by NIH Grant CA152879). Citation Format: Maarten C. Bosland, Michael J. Schlicht, Jillian Eskra, Zhongfa Liu. Inhibitory effects of black raspberry consumption on prostate carcinogenesis in rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2013-LB-185