Abstract 4611: Effect of pomegranate and diet on prostate cancer tumor growth and survival

Abstract

Abstract Background: Pomegranate extract (POM) has been shown to slow prostate cancer (PC) growth in xenograft models. However, mice in these studies ate standard mouse chow, which is very low-fat (∼12% kcals) and not representative of the typical diet for men with PC. Whether POM slows PC growth when taken with a Western diet is unknown. As our group showed diet to separately affect PC xenograft growth, with a no-carbohydrate ketogenic diet (NCKD) being protective vs. a Western diet, we tested the effects of POM on PC growth and survival in mice fed a Western or NCK diet. Methods: 120 male athymic nude mice (age 6-8 weeks) were fed an ad libitum Western diet and injected subcutaneously with 1×10⁁6 LAPC-4 cells. Two weeks later, mice were randomized to remain on Western diet alone or switched to Western diet + POM, NCKD alone, or NCKD + POM treatments (n=30 per arm). Western diet mice were fed ad libitum and NCKD mice via a modified pair-feeding protocol. POM arms received gavage with 0.8 mg POMx extract (PomWonderful) Monday-Friday and control mice received PBS (0.2 mL all arms). Mice were sacrificed when tumors exceeded 1,000 mm⁁3. Tumor volumes were compared between arms using Kruskal-Wallis. Survival between arms was tested using Cox proportional hazards. Results: The study is currently on-going and results are preliminary for day 53 post-injection. To date, significant differences in tumor volume have been noted across the study arms (p=0.007) with NCKD + POM mice having significantly smaller tumors than mice fed base Western diet (p=0.03). In mice fed NCKD, the addition of POM resulted in a trend toward smaller tumors (p=0.07). In contrast, in mice on Western diet, the addition of POM resulted in a trend toward larger tumors (p=0.13). Diet type alone did not affect tumor volume (p=1.00). Preliminary survival data suggest that treatment group impacted survival (p=0.055). Specifically, survival for the NCKD + POM arm was better than either Western + POM or NCKD alone arms (all p<0.046). Conclusion: In a xenograft mouse model, the combination of POM and dietary carbohydrate restriction slows PC tumor growth relative to a control Western diet and improves survival vs. either POM or NCKD treatments alone. Interestingly, our data show that POM delays tumor growth in mice fed NCKD but may actually accelerate tumor growth in mice fed a Western diet. Prior pomegranate studies reporting delayed tumor growth utilized very low-fat diets, which we have also shown to slow tumor growth vs. a Western diet, while our findings suggest that dietary background may profoundly influence the effect of pomegranate extract on PC tumor growth and survival. This is especially important given that men with PC are more likely to consume a Western diet. 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 4611. doi:10.1158/1538-7445.AM2011-4611