Enrichment of tomatoes and broccoli with specific bioactives for the reduction of prostate carcinogenesis.

摘要

Epidemiological studies have linked high consumption of tomatoes and cruciferous vegetables to decreased risk of prostate cancer. Several bioactive components isolated from cruciferous vegetables and tomatoes exhibit anti-cancer properties. Previous studies have evaluated the cancer preventive potential of these individual bioactives, but few have examined them within the context of a whole food.;In a pilot study to evaluate bioactivity of different tomato and broccoli powders, male Copenhagen rats were fed diets containing 10% standard tomato powder, tomato enriched with lycopene or total carotenoids, standard broccoli floret, broccoli sprouts, or broccoli enriched with indole glucosinolates or selenium for 7 days. All broccoli diets increased activity of colon quinone reductase (NQO1). Indole glucosinolate-enriched broccoli and selenium-enriched broccoli increased hepatic NQO1 and cytochrome P450 1A activity ( P 0.05). Different tomato diets resulted in altered hepatic accumulation of lycopene, phytofluene, and phytoene. These results demonstrate that the bioactive content of vegetables affects both tissue content of bioactives and activity of detoxification enzymes. Enhancing bioactive content of tomatoes and broccoli may enhance efficacy in the prevention of prostate cancer.;Based on the results of this pilot study, our next objective was to determine if standard broccoli or the indole glucosinolate-enriched (IG) broccoli, would impact prostate carcinogenesis in the aggressive TRAMP model. Male mice were randomized into 3 diet groups at 5--7 weeks of age: AIN-93G control, 10% control broccoli powder, or 10% IG broccoli powder. Diets were fed throughout the study until termination at 20 weeks of age, with no differences in body weight or food intake observed between groups. There were no differences between groups in genitourinary tract weight, a surrogate marker of tumor volume, and no differences were found in cancer grade upon histopathologic evaluation indicating that broccoli feeding did not impact cancer aggressiveness. The horticultural manipulation of broccoli to alter phytochemical concentration is a feasible approach to optimizing the potential for cancer prevention, yet optimal patterns of phytochemicals remain to be characterized.;To assess potential epigenetic effects of lycopene, we examined the effects of lycopene and its metabolite, apo-10'-lycopenal, on methylation of the GSTP1 promoter in LNCaP cells. GSTP1 is hypermethylated in >90% of prostate cancers, which results in complete silencing of the gene. Neither lycopene nor apo-10'-lycopenal altered mRNA expression or DNA methylation of GSTP1 indicating that lycopene is not an effective demethylating agent for this gene in this particular prostate cancer cell line. It remains to be seen if lycopene has epigenetic effects on other genes or in other cell lines.;Overall we have demonstrated that the bioactive content of tomatoes and broccoli can be altered through agronomic means, but optimal profiles for cancer prevention remain to be determined. Much remains to be learned about how tomatoes and broccoli alter cancer progression at different stages and the mechanisms through which they exert their effects.