Impact of Dietary Tomato on Prostate Carcinogenesis and Progression in Lean and Overweight/Obese TRAMP Mice

Abstract

Abstract Objectives The primary objective was to determine the effect of dietary tomato on prostate cancer (PCa) development and progression in overweight/obese, transgenic mice prone to PCa (TRAMP mice). Secondary objectives included assessing histological, inflammatory, angiogenic, and metabolic changes in prostate tumors at different time points of cancer progression. Methods Four-week-old TRAMP mice were randomly assigned to consume one of four diets (n = 45/diet): control (CON) or obesogenic (OB), both with and without 10% freeze-dried tomato powder (TP). Prostate tumor incidence and growth were monitored via ultrasound imaging. Mice were terminated one or four weeks following tumor development to assess early and later molecular changes in the tumors. Results OB diets led to greater body weight over time (45.2 ± 1.0 g at 24 weeks of age) when compared with CON diets (33.2 ± 0.8 g; p < 0.0001 by 2-way ANOVA), with TP inclusion having no impact on body weight within diets. OB diets resulted in greater tumor incidence (64.8% vs. 42.5%), earlier age at tumor onset (16.9 ± 1.0 weeks vs. 18.6 ± 0.7 weeks), higher body weight at tumor detection (38.6 ± 1.0 g vs. 30.8 ± 1.2 g), and greater post-mortem periprostatic adipose weight (2.0 ± 0.1 g vs. 0.9 ± 0.1 g). TP intake was protective only in lean animals, with CON-TP-fed animals having exhibited lower tumor volume at detection (28.7 ± 5.2 mm3 vs. 47.3 ± 15.5 mm3) and lower tumor weight at both one (0.1 ± 0.02 g vs. 0.2 ± 0.06 g) and four (1.5 ± 0.3 g vs. 2.1 ± 0.5 g) weeks following tumor detection compared with CON-fed animals. Conversely, TP was not protective in animals with obesity, with OB-TP-fed animals having exhibited no differences in tumor weight one week following tumor detection (0.3 ± 0.06 g vs. 0.3 ± 0.07 g) and greater tumor weight four weeks following tumor detection (2.5 ± 0.7 g vs. 2.0 ± 0.3 g) when compared with OB-fed animals. Conclusions TRAMP mice fed obesogenic diets have higher body weight and earlier onset of PCa. While tomato intake led to smaller tumors in lean animals, the opposite effect was observed in animals with higher body weight. Funding Sources This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.