A variety of epidemiological trials have suggested that higher intake of lycopene-containing foods (primarily tomato products) or blood lycopene concentrations are associated with decreased cardiovascular disease and prostate cancer risk. Of the carotenoids tested, lycopene has been demonstrated to be the most potent in vitro antioxidant leading many researchers to conclude that the antioxidant properties of lycopene are responsible for disease prevention. In our review of human and animal trials with lycopene, lycopene-containing extracts, or tomato products, there is limited support for the in vivo antioxidant function for lycopene. Moreover, tissue levels of lycopene appear to be too low to play a meaningful antioxidant role. We conclude that there is an overall shortage of supportive evidence for the “antioxidant hypothesis” as lycopene’s major in vivo mechanism of action. Our laboratory has postulated that metabolic products of lycopene, the lycopenoids, may be responsible for some of lycopene’s reported bioactivity.

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]

Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific components or combination of components in tomatoes that are responsible for reducing prostate cancer risk. We carried out cell culture trials to evaluate the effects of tomato carotenoids and tomato polyphenols on growth of prostate cancer cells. We also evaluated the ability of freeze-dried whole-tomato powder or lycopene alone to reduce growth of prostate tumors in rats. This paper reviews the epidemiological evidence, evaluating the relationship between prostate cancer risk and tomato consumption, and presents experimental data from this and other laboratories that support the hypothesis that whole tomato and its phytochemical components reduce the risk of prostate cancer.

In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function may be relevant to health, we hypothesize that metabolites of lycopene may be bioactive and responsible for the beneficial effects of tomato product consumption. We term these metabolites "lycopenoids," which we believe may be produced from carotenoid monooxygenase (CMO) II, paralleling the production of retinoids from beta-carotene by CMO I. We present evidence suggesting that tomato carotenoid metabolites may be responsible for the reduced risk of prostate cancer seen in men consuming high levels of tomato products. Finally, we identify gaps in knowledge in this evolving area of carotenoid research.