Combinations of Tomato and Broccoli Enhance Antitumor Activity in Dunning R3327-H Prostate Adenocarcinomas

Abstract

The consumption of diets containing 5 to 10 servings of fruits and vegetables daily is the foundation of public health recommendations for cancer prevention, yet this concept has not been tested in experimental models of prostate cancer. We evaluated combinations of tomato and broccoli in the Dunning R3327-H prostate adenocarcinoma model. Male Copenhagen rats (n = 206) were fed diets containing 10% tomato, 10% broccoli, 5% tomato plus 5% broccoli (5:5 combination), 10% tomato plus 10% broccoli (10:10 combination) powders, or lycopene (23 or 224 nmol/g diet) for f22 weeks starting 1 month prior to receiving s.c. tumor implants. We compared the effects of diet to surgical castration (2 weeks before termination) or finasteride (5 mg/kg body weight orally, 6 d/wk). Castration reduced prostate weights, tumor areas, and tumor weight (62%, P < 0.001), whereas finasteride reduced prostate weights (P < 0.0001), but had no effect on tumor area or weight. Lycopene at 23 or 224 nmol/g of the diet insignificantly reduced tumor weights by 7% or 18%, respectively, whereas tomato reduced tumor weight by 34% (P < 0.05). Broccoli decreased tumor weights by 42% (P < 0.01) whereas the 10:10 combination caused a 52% decrease (P < 0.001). Tumor growth reductions were associated with reduced proliferation and increased apoptosis, as quantified by proliferating cell nuclear antigen immunohistochemistry and the ApopTag assay. The combination of tomato and broccoli was more effective at slowing tumor growth than either tomato or broccoli alone and supports the public health recommendations to increase the intake of a variety of plant components. [Cancer Res 2007;67(2):836-43]

A Dietary Tomato Supplement Prevents Prostate Cancer in TRAMP Mice

“…In rats, tomato supplementation reduces carcinogenesis-induced mortality more efficiently than lycopene (13)(14)(15). Again, in the Dunning R3327-H prostate cancer model, the intake of whole foods, such as tomatoes and broccoli, slowed tumor growth more effectively than lycopene alone (16). Tomatoes contain other anticancer phytochemicals [see U.S. Department of Agriculture National Nutrient Database for Standard Reference: release 19 (2006), pdf available from http://www.nal.usda.gov/fnic/ foodcomp/cgi-bin/measure.pl?MSRE_NO=11548xyz1100 xyzTomato%20powderxyzxyz], whereas constituents already present in small amounts or newly formed during processing also contribute to their final in vivo efficacy (14).…”

Phytoene, phytofluene, and lycopene from tomato powder differentially accumulate in tissues of male Fisher 344 rats

“…Our laboratory has demonstrated in an N-methyl-N-nitrosurea (MNU)-androgen induced rat carcinogenesis model and in a Dunning R-3327H transplantable prostate adenocarcinoma model, that diets containing 10% whole tomato powder significantly inhibited the development of prostate cancer as compared to a control diet, whereas a LYC-supplemented diet was not as effective [11,12]. Short-term clinical studies with prostate cancer patients have reported therapeutic benefits with tomato supplementation, including reductions in prostate size, leukocyte DNA damage, and prostate specific antigen levels, as well as positively modulated volume and grade of prostate intraepithelial neoplasia, and also altered biomarkers of prostate cell growth and differentiation [13,14].…”

The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action

“…Using the same animal model it was found that fed male Copenhagen rats with diets containing 10% broccoli, decreased tumor weight by 42%. Tumor growth reduction was associated with reduced proliferation and increased apoptosis [87]. Moreover, treatment of mice with DIM inhibits tumor formation of TRAMP cells, mouse prostate cancer cells [88].…”