Abstract 5631: The effect of pomegranate extract dose on prostate cancer growth in a carbohydrate restricted mouse xenograft model

Introduction: Preclinical studies have shown that dietary carbohydrate restriction slows prostate tumor growth in multiple xenograft models in part due to a reduction insulin-like growth factor (IGF) axis signaling. Pomegranate extract (PE) has been shown to slow prostate tumor growth in-vitro and in vivo similarly through this pathway, as well as decrease markers of angiogenesis and inflammation. In this study, we determined the dose-response of PE on prostate tumor growth in the setting of dietary carbohydrate restriction in a slow-growing mouse xenograft model. For this study, we chose a standardized PE (POMx, Pom Wonderful, Los Angeles, CA), at doses which are easily translatable to human equivalents. Materials and Methods: Male athymic nude mice housed 5 per cage (n = 130) were subcutaneously injected with 1 × 10^5 LAPC-4 cells after a 10 day acclimation period. 14 days post-injection, all mice were all placed on an ad-libitum no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein) (day 0). Each cage was randomly assigned to 1 of 4 doses of PE (placebo = 0 mg, low dose = 2.62 mg, intermediate dose = 5.25mg, or high dose = 7.87mg) suspended in 0.2 mL of PBS delivered via oral gavage 5 days per week. These doses are equivalent to 0, 1, 2, or 3 POMx capsules/day consumed by a 70 kg human. Mice will be sacrificed when tumors reach ≥1,000 mm^3. Results: At randomization, there were no differences in median body weight among groups (p = 0.623). Currently, at day 32, overall survival is decreased in the placebo group (hazard ratio 2.26, 95% confidence interval, 0.83 - 6.10, p = 0.109) relative to the low dose PE group with no survival differences among PE groups. Median tumor volumes for the placebo group are 83.3mm^3, compared to 74.5mm^3, 76.3mm^3, and 70.1mm^3 for the low, intermediate, and high PE doses respectively, which are not statistically different (p = 0.98). Conclusions: Preliminary data show a trend toward improved survival with the combination of an NCKD and PE at the selected doses. Currently, tumor volumes are not significantly different, however completed results will be presented.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5631. doi:1538-7445.AM2012-5631

Duke Scholars

Author Michael R Abern Urology