Abstract 2800: Dietary black raspberries (BRBs) inhibit tumor progression in PTEN-deficient mouse model of prostate cancer

Abstract

Abstract Black raspberries (BRBs) a natural food demonstrated to have anti-oxidant, anti-inflammatory and anti-cancer activities,have been shown to inhibit oral, esophageal, mammary gland and colon cancers in rodents. Several human trials have been completed to date to assess the efficacy of BRB formulations for cancer prevention. However, the chemopreventive potential of BRBs against prostate cancer, the most commonly diagnosed malignancy and the second leading cause of death among men in the United States, is yet to be reported. Among the murine models, PTEN-mutant mice develop tumors in situ that faithfully mimic the intratumor heterogeneity observed during the progression of human prostate cancer. Therefore, we utilized this clinically relevant PTEN-mutant mouse model to evaluate the chemopreventive potential of BRBs against prostate cancer. Genotyped 5-week-old male PTEN-mutant mice, randomly assigned to control and treatment groups (n = 12 mice/group), were fed AIN-93G diet (control) or AIN-93G diet supplemented with BRBs (5 or 10%) for 23 weeks. Age-matched non-transgenic mice (wild-type) served as experimental controls (n = 6). Animal weight and food consumption were measured during the treatment period, and the mice were euthanized at 28 weeks of age. Prostate tissues were harvested, weighed and fixed in 10% formalin for histopathological analysis. Histological, cell proliferation (Ki-67 staining) and apoptosis (TUNEL) analyses were performed to determine the chemopreventive potential of BRBs. PTEN-mutant mice fed control or BRB (5 or 10%) diets had steady body weight gain, 16 to 18 g during the 23-week treatment. BRB diets were well tolerated as none of the animals fed BRBs exhibited any observable toxicity. PTEN-mutant mice (control) had increased prostate weight (ave. = 248 mg) relative to wild-type mouse prostate (ave. = 90 mg), and 5 and 10% BRB diets significantly (p<0.01) decreased the prostate weights to ave. = 116 and 162 mg, respectively, compared to control. In addition, 5% BRBs significantly (p<0.05) reduced the prostate weights compared to 10% BRBs. Histological examination of dorsolateral prostate (DLP) revealed that 98% of PTEN-mutant mice fed control diet developed invasive adenocarcinomas, whereas both 5 and 10% BRB diets significantly reduced tumor incidence and the progression of PIN lesions to invasive adenocarcinomas by 64% (p<0.0001) and 43% (p<0.001), respectively. Interestingly, 5% BRBs appear to be more effective than 10% BRBs (p<0.01). Both 5 and 10% BRBs significantly reduced tumor cell proliferation rates and induced apoptosis, p<0.0001 and p<0.001, respectively. Furthermore, mice fed both 5 and 10% BRBs contained more normal appearing prostates (free from PIN lesions and adenocarcinomas), when compared to control mice (54 and 33% compared to 3%, respectively). In conclusion, our data indicate that BRBs may have significant potential for prostate cancer prevention and/or treatment. Citation Format: Narayanan K. Narayanan, Gary D. Stoner, Daniel S. Peiffer, Karen Galdanes, Eric Larios, Alu Mark, Lisa Maziniski, Luis Chiriboga, Maarten C. Bosland. Dietary black raspberries (BRBs) inhibit tumor progression in PTEN-deficient mouse model of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2800. doi:10.1158/1538-7445.AM2015-2800