Dietary interventions for reduction of prostate carcinogenesis in rodent models

Prostate cancer (PCa) is the second leading cause of cancer and cancer related deaths in U.S. men; thus, identifying strategies to reduce PCa incidence could have a significant impact on public health. Epidemiological studies have supported the hypotheses that dietary intake of soy foods or tomato products is associated with a reduced risk of PCa. The efficacy of combinations of foods and bioactives for enhanced health benefits is of clinical interest, but the interactions between foods rich in bioactives for the inhibition of PCa are largely unknown. To evaluate the bioavailability of tomato carotenoids and soy germ isoflavones when consumed alone or together, male Copenhagen rats were randomized to consume: AIN-93G control, 10% tomato powder (TP), 2% soy germ (SG) or 10% tomato powder + 2% soy germ (TP+SG) for 7 days or 25 weeks. In the 7-day trial, rats consuming TP+SG had significantly lower serum phytoene, phytofluene, and lycopene compared to rats consuming TP alone (p<0.05). In the 25-week trial, lycopene bioaccumulation was significantly lower in the testes, seminal vesicles and ventral prostate of rats that consumed TP+SG compared to TP alone (p<0.05). Reduced carotenoid bioaccumulation was not explained by mRNA expression of scavenger receptor class B type I (a protein involved in carotenoid absorption) or carotenoid metabolizing enzymes in the prostate, liver or duodenal mucosa. Hepatic lipid accumulation and serum cholesterol were not significantly different between groups, suggesting that differences in carotenoid bioaccumulation were likely not due to effects on intestinal micellerization or lipid absorption. Significantly higher urinary isoflavone excretion in the TP+SG group compared to the SG group was not explained by differences in activity or expression of hepatic detoxification enzymes. Soy isoflavones and tomato carotenoids have distinctly different mechanisms of absorption, yet, long-term combined consumption of TP+SG resulted in reduced carotenoid bioaccumulation and increased urinary isoflavone excretion than when each food was consumed separately. After identifying a food-food interaction in the bioavailability study, the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of PCa was evaluated in the TRAMP model of PCa. At 4 weeks of age, male TRAMP mice were randomized to consume: AIN-93G control, 10% TP, 2% SG or TP+SG for 14 weeks. Serum and testicular lycopene concentrations were significantly lower in TP+SG fed mice compared to mice fed TP alone, supporting our previous finding of reduction of carotenoid bioavailability by consumption of SG. Equol, produced from the metabolism of daidzein by intestinal microbiota, was the predominant isoflavone in the serum and prostate in SG fed mice. 100% of mice fed the control diet had PCa, while PCa incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p