No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Tomato, Broccoli, Soy and Reduced Prostate Cancer Risk: Whole Foods or Their Bioactive Components?
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in U.S. men. PCa is a slow-growing cancer; therefore, identifying dietary interventions to reduce the risk or progression of PCa could greatly impact public health. A growing body of evidence has identified several foods that may reduce the risk of PCa. Mechanistic studies have investigated individual bioactives from foods to identify their anticarcinogenic properties; however, it is also important to study the whole food. In rodent models of PCa, we have shown that consumption of whole tomato powder was more effective than lycopene alone in reducing PCa progression. In a transgenic mouse model of PCa, broccoli consumption significantly altered expression of genes involved in the epithelial-mesenchymal transition, which may be a mechanism by which broccoli intake has been associated with a reduced risk of aggressive PCa. Combinations of foods may be more protective than individual foods, but this should not be assumed, as antagonistic activity between bioactives has been suggested. We have investigated the combinations of tomato and broccoli and tomato and soy germ. Future diet and cancer research should continue to focus on whole foods and combinations of foods for better translation into recommendations for the public.
Consumption of tomato products or lycopene and energy restriction have been hypothesized to reduce the risk of human prostate cancer. We investigated the effects of these dietary variables in a rat model of prostate carcinogenesis.
Male rats (n = 194) treated with N-methyl-N-nitrosourea and testosterone to induce prostate cancer were fed diets containing whole tomato powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or control beadlets. Rats in each group were randomly assigned to either ad libitum feeding or 20% diet restriction. Differences between Kaplan-Meier survival curves for diet composition or restriction were tested with the log-rank test. Cox proportional hazards models were developed to examine the combined effect of diet composition and restriction on survival. Statistical tests were two-sided.
Risk of death with prostate cancer was lower for rats fed the tomato powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.59 to 0.93; P =.009). In contrast, prostate cancer-specific mortality of the control and lycopene-fed rats was similar (P =.63). The proportions of rats dying with prostate cancer in the control, lycopene, and tomato powder groups were 80% (95% CI = 68% to 89%), 72% (95% CI = 60% to 83%), and 62% (95% CI = 48% to 75%), respectively. Rats in the diet-restricted group experienced longer prostate cancer-free survival than rats in the ad libitum-fed group (HR = 0.68, 95% CI = 0.49 to 0.96; P =.029). The proportion of rats that developed prostate cancer was 79% (95% CI = 69% to 86%) for ad libitum-fed rats and 65% (95% CI = 54% to 74%) for rats fed restricted diets. No interactions were observed between diet composition and dietary restriction.
Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis, suggesting that tomato products contain compounds in addition to lycopene that modify prostate carcinogenesis. Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms.
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 approximately 22 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.
Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.
Consumption of fruits and vegetables has generally been associated with a decrease in cancer incidence and cardiovascular disease. Over the years, numerous bioactive compounds have been identified that contribute to these beneficial health effects. More recently, evidence is emerging that specific combinations of phytochemicals may be far more effective in protecting against cancer than isolated compounds. Combinatorial effects have been observed where any one of the single agents is inactive. Apart from interactions among dietary micronutrients, drug-phytochemical interactions have also been observed, indicating possibilities for improved cancer therapeutic strategies. Our understanding of the molecular mechanisms underlying such synergistic effects is still limited, but it appears that different combinations of complementary modes of actions are involved. In this review, we discuss the molecular mechanisms that are likely to be involved in cancer chemoprevention and summarize the most important findings of those studies that report synergistic chemopreventive effects of dietary compounds.
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,596,670 new cancer cases and 571,950 deaths from cancer are projected to occur in the United States in 2011. Overall cancer incidence rates were stable in men in the most recent time period after decreasing by 1.9% per year from 2001 to 2005; in women, incidence rates have been declining by 0.6% annually since 1998. Overall cancer death rates decreased in all racial/ethnic groups in both men and women from 1998 through 2007, with the exception of American Indian/Alaska Native women, in whom rates were stable. African American and Hispanic men showed the largest annual decreases in cancer death rates during this time period (2.6% and 2.5%, respectively). Lung cancer death rates showed a significant decline in women after continuously increasing since the 1930s. The reduction in the overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 898,000 deaths from cancer. However, this progress has not benefitted all segments of the population equally; cancer death rates for individuals with the least education are more than twice those of the most educated. The elimination of educational and racial disparities could potentially have avoided about 37% (60,370) of the premature cancer deaths among individuals aged 25 to 64 years in 2007 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population with an emphasis on those groups in the lowest socioeconomic bracket.
The efficacy of combinations of food for enhanced anticancer activity is of clinical interest, but there is limited information on the effect of combined consumption on bioactive bioavailability. Male Copenhagen rats consumed diets containing 10% tomato powder (TP), 2% soy germ (SG), neither, or a combination (TP+SG) for 25 weeks (n = 63) or 7 days (n = 24). After 7 days, serum carotenoids were significantly lower after TP+SG feeding compared to TP alone. After 25 weeks, the TP+SG group had significantly lower lycopene and β-carotene concentration in the testes, seminal vesicles, and ventral prostate compared to the TP group and significantly higher urinary isoflavone excretion compared to the SG group. These differences were not explained by mRNA expression of scavenger receptor class B type I, carotene 15,15'-monooxygenase I, carotene 9',10'-monooxygenase II, or activity of hepatic detoxification enzymes. The results suggest interactions between soy germ and tomato powder that enhance isoflavone absorption but reduce carotenoid bioavailability.
Over the past several decades, research on the action of bioactive constituents of plants has focused predominantly on their cancer-preventive properties. Today it can be explained why the consumption of fruits and vegetables may lead to a reduced frequency of certain cancer entities and why certain foods have therapeutic effects. Secondary plant products and especially glucosinolates from vegetables of the cruciferae family are supposed to have anti-carcinogenic potential. The present article gives an overview about secondary plant products in general and focuses to mechanisms of preventive and therapeutic effects of cruciferae, particular the brassica family and their famous member broccoli. Also, this article summarizes our knowledge of safety, tolerance and metabolism of glucosinolates and their therapeutic active degradation products isothiocyanates in animals and clinical studies.
Research and practice in nutrition relate to food and its constituents, often as supplements. In food, however, the biological constituents are coordinated. We propose that "thinking food first"' results in more effective nutrition research and policy. The concept of food synergy provides the necessary theoretical underpinning. The evidence for health benefit appears stronger when put together in a synergistic dietary pattern than for individual foods or food constituents. A review of dietary supplementation suggests that although supplements may be beneficial in states of insufficiency, the safe middle ground for consumption likely is food. Also, food provides a buffer during absorption. Constituents delivered by foods taken directly from their biological environment may have different effects from those formulated through technologic processing, but either way health benefits are likely to be determined by the total diet. The concept of food synergy is based on the proposition that the interrelations between constituents in foods are significant. This significance is dependent on the balance between constituents within the food, how well the constituents survive digestion, and the extent to which they appear biologically active at the cellular level. Many examples are provided of superior effects of whole foods over their isolated constituents. The food synergy concept supports the idea of dietary variety and of selecting nutrient-rich foods. The more we understand about our own biology and that of plants and animals, the better we will be able to discern the combinations of foods, rather than supplements, which best promote health.
Epidemiological studies have yielded conflicting results on the associations of diet with prostate cancer. We review evidence that Brassica vegetables are associated with reduced prostate cancer risk. Brassica vegetables, which include broccoli, cabbage, mustard and collard greens, and bok choy, contain glucosinolates, the metabolic breakdown products of which are potent modulators of xenobiotic-metabolizing enzymes that protect DNA from damage. Twelve published studies give some information about Brassica vegetables and prostate cancer risk; six of these studies can be clearly interpreted. Of these, three reported statistically significant reduced risks (P < 0.05) and one reported a borderline significant reduced risk (P = 0.06) with high Brassica vegetable consumption. The epidemiological literature provides modest support for the hypothesis that high intakes of Brassica vegetables reduce prostate cancer risk.
Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in human prostate cancer. We here present novel data, with special focus on the independent relationship between an E-cadherin to N-cadherin switch (EN-switch) and patient prognosis.
Tissue microarray sections from a consecutive series of 104 radical prostatectomies during 1988 to 1994 with detailed clinicopathologic data and long follow-up were studied immunohistochemically for the expression of E-cadherin, N-cadherin, P-cadherin, beta-catenin, and p120(CTN).
Low E-cadherin expression was significantly associated with adverse clinicopathologic features, whereas other biomarkers were mostly related to Gleason score. In univariate survival analyses, cadherin switching (high N-cadherin and low E-cadherin) showed strong and significant associations with multiple end points of progression and cancer-specific death. Expression of the "basal cell marker" P-cadherin was associated with shorter time to skeletal metastasis (P = 0.036). In multivariate analysis of time to clinical recurrence, the "EN-switch" (hazard ratio, 4.3; P < 0.0005) had strong and independent prognostic effect, together with Gleason score.
These novel data unravel the importance of epithelial to mesenchymal transition for prostate cancer progression, and demonstration of a switch from E-cadherin to N-cadherin expression could have significant effect on the care of prostate cancer patients.
Epithelial-mesenchymal transition (EMT) is a key step during embryonic morphogenesis, heart development, chronic degenerative
fibrosis, and cancer metastasis. Several distinct traits have been conveyed by EMT, including cell motility, invasiveness,
resistance to apoptosis, and some properties of stem cells. Many signal pathways have contributed to the induction of EMT,
such as transforming growth factor-β, Wnt, Hedgehog, Notch, and nuclear factor-κB. Over the last few years, increasing evidence
has shown that EMT plays an essential role in tumor progression and metastasis. Understanding the molecular mechanism of EMT
has a great effect in unraveling the metastatic cascade and may lead to novel interventions for metastatic disease.