Tomatoes and tomato products are now being investigated for their potential role in prostate cancer prevention and therapy.
This review summarizes the in vitro and in vivo evidence as well as the molecular data that show the anticarcinogenic potential of tomatoes.Raw and processed tomatoes are among the most commonly consumed vegetables. They are rich in the phytochemicals carotenoids and
polyphenols. Lycopene and quercetin are the most abundant carotenoids and flavonols respectively. Canned tomato sauce is the primary source of lycopene whereas the tomato skin is enriched with flavonols. Most epidemiological studies suggest that the consumption of tomatoes and their products is associated with a reduced prostate cancer risk. The Health Professionals Follow-Up Study found that men who consumed 2 to 4 servings of raw tomatoes per week had a more than 20% reduction in prostate cancer risk compared to men who did not consume tomatoes. The prostate cancer risk was reduced by 35% in men who consumed 10 or more servings per week of tomatoes or their processed products compared to those who consumed less than 1.5 servings per week. Nested, case-control data from a follow-up study found an inverse correlation between lycopene concentrations and cancer risk that appeared particularly striking in men 65 years of age or older and in those with no family history of prostate cancer. This suggests that sporadic cancer cases are more susceptible to tomatoes and lycopene than are genetic causes of cancer. High lycopene plasma concentrations were associated with a low incidence of prostate cancer and aggressive prostate cancer in a nested case-control study within the Physicians’ health Study. The relationship was not found for any other carotenoid or tocopherol studied. A meta-analysis of 21 studies found that prostate cancer risk was reduced significantly only when men with the highest and lowest quintile of tomato and tomato product intakes were compared. While this suggests a modest effect of tomatoes on cancer risk, the data does support the conclusion that tomatoes are a good source of anticarcinogenic
compounds.In vitro data show that the compounds found in tomatoes are potent anticarcinogens. Cancer cell growth is inhibited by the polyphenols quercetin, kaempferol and naringenin in a dose-dependent manner. These compounds do not have cytotoxic effects. In a rat model of prostate cancer, tomato powder intake but not lycopene intake by itself reduced prostate cancer -related mortality. This suggests that the compounds in tomatoes have an additive influence on prostate cancer. In a less differentiated but aggressive prostate cancer cell model, rats fed vitamine E alone or in combination with lycopene increased necrotic tumor tissue mass. This suggests that tomatoes have an androgen-dependent mechanism.Lycopenes exist as either the cis or trans isomer. The half-life of lycopene is approximately 10 to 14 days, so it remains in the body during a washout period. The trans isomer dominates in tomatoes, but the cis isomer dominates in serum and tissues and during a washout period. Thus, recent intake of lycopenes is reflected in blood concentrations whereas long-term exposure is determined in the tissues. Both isomers are found in prostate cancer cells, but the specific role of each in cancer prevention is not known.Clinical trials support the anticarcinogenic potential of tomatoes. Prostate cancer cells accumulate both lycopene isomers when patients are fed tomato sauce. Dietary intervention reduces prostate tissue oxidative damage and prostate-specific antigen concentrations in prostate cancer patients compared to untreated controls. A small study showed that tomato supplementation positively modulated the volume and grade of prostate intraepithelial neoplasia in patients awaiting radical prostectomy. Larger, randomized clinical trials are needed to confirm these promising results.Tomatoes could reduce carcinogenic potential through a varietyof mechanisms. Carotenoids and polyphenols are antioxidants and clinical trials demonstrate that they do indeed reduce oxidative damage in vivo. They influence Phase I and II drug-metabolizing enzymes. For example, flavonoids inhibit cytochrome 1A isoforms which are implicated in the carcinogenesis of many compounds. Insulin-like growth factor and other growth or hormone factors are sensitive to carotenoids and polyphenols. Interfering with the action of these factors would reduce the potential for cell proliferation. Finally, lycopene prevents cell cycle progression and upregulates a protein involved in cell-to-cell communication, connexin 43. These antineoplastic properties of compounds found in tomatoes as well as the preliminary clinical data support the further investigation of tomatoes and their products as cancer therapies.