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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.5631-5631
• Main Authors: Abern, Michael R., Masko, Elizabeth M., Wu, Chenwei, Gaines, Alexis R., Pizzo, Salvatore, Freedland, Stephen J.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-5631

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