Abstract 840: Pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP mouse model

Abstract

Abstract Pomegranate fruit extract (PFE) dubbed as “nature's power fruit” was found to prolong prostate specific antigen (PSA) doubling time in men with rising PSA after surgery and therapy and hailed as a promising non-toxic strategy for slowing the progression of prostate cancer (PCa). To ascertain conclusive evidence of the effects of PFE against PCa require its efficacy evaluation in animal models that closely emulate human disease. Here, we provide evidence of remarkable tumor growth inhibitory effects using TRAMP, an autochthonous transgenic mouse model that mimics progressive forms of human PCa. Mice were supplied with 0.1% and 0.2% PFE as the sole source of drinking fluid starting at the age of 6 weeks. This drinking regimen is based on the assumption that a typical healthy individual (70 kg) may be persuaded to drink 250 or 500 ml of PFE from one or two fruits, respectively. Animals were examined at 12, 20 and 34 weeks of age for prostate tumor growth. In water-fed group, 100% mice developed palpable tumors by 20 weeks of age compared to only 30% and 20% in the 0.1% and 0.2% PFE-fed groups, respectively as assessed by abdominal pelvic palpation, MRI and ultrasound based imaging. At 34 weeks of age palpable tumors were observed in 70% of 0.1% PFE fed and only 50% of 0.2% PFE-fed TRAMP mice. Compared to a median survival of 43 weeks in water-fed mice, PFE-fed mice exhibited significant increase in life span with 0.1% and 0.2% PFE-fed mice exhibiting median life expectancy of 73 and 92 weeks, respectively. The cumulative data on metastasis at 20 and 34 weeks of age in the water-fed group showed 30% and 90% incidence of invasive tumors, which had metastasized to the lungs and liver. In sharp contrast, in the 0.1% and 0.2% PFE-fed group, none of the 20 mice exhibited metastases to any of the distant organs studied at 20 weeks of age and only 20% mice exhibited metastasis at 34 weeks of age. PFE feeding resulted in significant decrease in hyperplasia in the genitourinary (GU) apparatus, especially in the seminal vesicles. A significant decrease in GU weight (∼68% in 0.1% PFE and ∼79% in 0.2% PFE) compared with the water-fed TRAMP group was observed. At 34 weeks of age prostates of PFE-fed TRAMP mice contained well-differentiated adenocarcinoma that occupied ∼20% at surface area, admixed with lesser amounts of moderately differentiated adenocarcinoma (<3% of surface area), histology that was comparable to controls at 12 weeks of age. Many of the PFE-fed animals had multiple foci of well differentiated carcinoma (10-20% of surface area) and some had poorly differentiated carcinoma. PFE feeding resulted in simultaneous and significant inhibition of the IGF-I/Akt/mTOR pathways in the prostate tissues and tumors. This is significant since such a combined inhibition is seen only with a combination of drugs and not with a single agent alone. We suggest that pomegranate juice be evaluated in clinical trials in patients at high risk for developing prostate cancer. 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 840. doi:10.1158/1538-7445.AM2011-840