To examine how tomato consumption may impact the development of prostate cancer, we looked for significant relationships between diet and prostate cancer in nearly 28, Adventist men in the US.

All Adventist Health Study participants agree to fill out self-administered food frequency questionnaires reporting the average number of times per week they ate approximately different foods and beverages, and the serving sizes.

As we focused on dietary lycopene levels, we found that men who consumed canned and cooked tomatoes five to six times a week had a 28 per cent decreased risk of prostate cancer compared with men who never consumed this food. The effect was still significant even after adjusting for potential confounders including ethnicity, education, obesity, exercise levels, alcohol consumption and others.

Interestingly, we found no significant association between prostate cancer and consumption of raw tomatoes, tomato soup, tomato sauce and tomato-based vegetable juice.

While all tomatoes and tomato-based products contain lycopene, other studies have shown that lycopene is absorbed at different rates depending on the product consumed. Lycopene bioavailability is higher when tomatoes have been heated or cooked, and especially if cooked with oil.

Processing tomatoes in this way contributes to the separation of the lycopene from the carrier proteins. It may be their lycopene content that is the active principle. We will continue to look at tomato products and their potential to reduce prostate cancer risk.

Still, men concerned about developing prostate cancer could consider adding cooked and canned tomatoes to their diet on a regular basis. View all latest articles. Close Menu Diet, activity and cancer. Global Cancer Update Programme. Cancer types.

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What we are funding. Research highlights. By the end of the study, serum PSA levels had almost doubled in 12 of the 17 patients, and 5 of 17 patients had achieved PSA stabilization.

Although this was a small study without a control group , the results suggest that lycopene may not be beneficial for patients with advanced prostate cancer.

Only one patient in this study exhibited a decrease in PSA level. Several episodes of gastrointestinal side effects were noted after eating the tomato paste or drinking the tomato juice. Perhaps, future clinical trials should include longer duration of consistent lycopene exposure, while accounting for variations in individual absorption of carotenoids and heterogeneity of high-risk HGPIN, atypical small acinar proliferation and prostate cancer patient populations indolent vs.

aggressive prostate cancer or androgen-dependent vs. androgen-independent prostate cancer. Studies evaluating lycopene in randomized clinical trials targeting men at high risk for prostate cancer and populations with prostate cancer have indicated relatively few toxicities at the dose and duration of intervention.

When adverse effects occurred, they tended to present as gastrointestinal symptoms [ 49 ] and, in one study, the symptoms resolved when lycopene was taken with meals. Pectin is a complex polysaccharide contained in the primary cell walls of terrestrial plants.

The word pectin comes from the Greek word for congealed or curdled. Plant pectin is used in food processing as a gelling agent also in the formulation of oral and topical medicines as a stabilizer and nonbiodegradable matrix to support controlled drug delivery.

Some research suggests that MCP may be protective against various types of cancer, including colon , lung , and prostate cancer. MCP may exert its anticancer effects by interfering with tumor cell metastasis or by inducing apoptosis.

MCP was also shown to activate natural killer cells in leukemic cell cultures, suggesting it may be able to stimulate the immune system. Several companies distribute MCP as a dietary supplement.

The FDA has not approved the use of MCP as a treatment for cancer or any other medical condition. In a study, pectins were investigated for their anticancer properties. Prostate cancer cells were treated with three different pectins; CP, Pectasol PeS, a dietary supplement containing MCP , and fractionated pectin powder FPP.

FPP induced apoptosis to a much greater degree than did CP and PeS. Further analysis revealed that treating prostate cancer cells with heated CP resulted in levels of apoptosis similar to those following treatment with FPP.

This suggests that specific structural features of pectin may be responsible for its ability to induce apoptosis in prostate cancer cells. In a study, prostate cancer cells were treated with PeS or PectaSol-C, the only two MCPs previously used in human trials. The researchers postulated that, because it has a lower molecular weight, PectaSol-C may have better bioavailability than PeS.

In one study, the role of galectin-3, a multifunctional endogenous lectin , in cisplatin -treated prostate cancer cells was examined. Prostate cancer cells that expressed galectin-3 were found to be resistant to the apoptotic effects of cisplatin.

However, cells that did not express galectin-3 via silencing RNA knockdown of galectin-3 expression or treatment with MCP were susceptible to cisplatin-induced apoptosis. These findings suggest that galectin-3 expression may play a role in prostate cancer cell chemoresistance and that the efficacy of cisplatin treatment in prostate cancer may be improved by inhibiting galectin Only a few studies have been reported on the effects of MCP in animals bearing implanted cancers and only one involving prostate cancer.

In the study, rats were given 0. The analysis revealed that treatment with 0. In a pilot study , patients with advanced solid tumors various types of cancers, including prostate cancer received MCP 5 g MCP powder dissolved in water 3 times a day for at least 8 weeks.

Following treatment, improvements were reported in some measures of quality of life , including physical functioning, global health status, fatigue , pain, and insomnia. In addition, The effect of MCP on prostate-specific antigen PSA doubling time PSADT was investigated in a study. Prostate cancer patients with rising PSA levels received six PeS capsules 3 times a day totaling In one prospective pilot study , MCP was well tolerated by the majority of treated patients, with the most commonly reported side effects being pruritus , dyspepsia , and flatulence.

The pomegranate tree Punica granatum L. is a member of the Punicaceae family native to Asia from Iran to northern India and cultivated throughout the Mediterranean, Southeast Asia, the East Indies, Africa, and the United States. The arils are mainly composed of water and also contain phenolics and flavonoids.

Anthocyanins, which are flavonoids present in arils, are responsible for the red color of the fruit and its juice. Research studies suggest that pomegranates have beneficial effects on a number of health conditions, including cardiovascular disease,[ 6 ] and may also have positive effects on oral or dental health.

Several companies distribute pomegranate as a dietary supplement. The FDA has not approved the use of pomegranate as a treatment or prevention for cancer or any other medical condition. Research studies in the laboratory have examined the effects of pomegranate on many prostate cancer cell lines and in rodent models of the disease.

Ellagitannins the main polyphenols in pomegranate juice are hydrolyzed to ellagic acid , and then to urolithin A UA derivatives. According to a tissue distribution experiment in wild-type mice, the prostate gland rapidly takes up high concentrations of UA after oral or intraperitoneal administration 0.

Ellagic acid EA was detected in the prostate following intraperitoneal, but not oral, administration of pomegranate extract 0. Treating human prostate cancer cells with individual components of the pomegranate fruit has been shown to inhibit cell growth.

Treating cells with EGCG, kaempferol, and punicic acid further resulted in apoptosis, with punicic acid a major constituent of pomegranate seeds being the strongest inducer of apoptosis.

Additionally, findings from this study suggested that punicic acid may activate apoptosis by a caspase-dependent pathway.

Pomegranate extracts have also been shown to inhibit the proliferation of human prostate cancer cells in vitro. All four treatments resulted in statistically significant increases in apoptosis and dose-dependent decreases in cell proliferation in the three cell lines.

However, PJ and POMx were stronger inhibitors of cell growth than were PA and EA. In this study, the effects of PA, EA, POMx, and PJ on the expression of androgen -synthesizing enzyme genes and the androgen receptor were also measured.

Although statistically significant decreases in gene expression occurred in LNCaP cells following treatment with POMx and in DU cells following treatment with EA and POMx, significant decreases in gene expression and androgen receptor occurred in LNCaP-AR cells following all of the treatments.

The enzyme cytochrome P CYP1B1 has been implicated in cancer development and progression. As a result, CYP1B1 inhibitors may be effective anticarcinogenic targets.

In a study reported in , the effects of pomegranate metabolites on CYP1B1 activation and expression in CWR22Rv1 prostate cancer cells were examined. In this study, urolithins A and B inhibited CYP1B1 expression and activity.

In addition, the insulin-like growth factor IGF system has been implicated in prostate cancer. A study reported in examined the effects of a POMx on the IGF system. However, these substances may have induced apoptosis by different mechanisms. Other findings suggested that POMx treatment reduced mTOR phosphorylation at Ser and Ser, whereas IGFBP-3 increased phosphorylation at those sites.

The results showed that treatment with PJ increased adhesion and decreased the migration of prostate cancer cells. Molecular analyses revealed that PJ increased the expression of cell-adhesion related genes and inhibited the expression of genes involved in cytoskeletal function and cellular migration.

These findings suggested that PJ may be beneficial in slowing down or preventing cancer cell metastasis. The effects of pomegranate on prostate cancer have been examined using a number of rodent models of the disease. In one study, athymic nude mice were injected with tumor-forming cells.

Following inoculation, animals were randomly assigned to receive normal drinking water or PJ 0. Small, solid tumors appeared earlier in mice drinking normal water only than in mice drinking PJ 8 days vs. Moreover, tumor growth rates were significantly reduced in mice drinking PJ compared with mice drinking normal water only.

Animals drinking PJ also exhibited significant reductions in serum PSA levels compared with animals drinking normal water only. In a study reported in , 6-week-old transgenic adenocarcinoma of the mouse prostate TRAMP mice received normal drinking water or PJ 0.

The PJ-supplemented mice exhibited significantly increased life spans compared with the water-fed mice. Three clinical studies have examined the effect of interventions with pomegranate products on changes in PSADT in patients with biochemically recurrent prostate cancer who had a rising PSA level after surgery or radiation therapy for presumed localized cancer.

Overall, median PSADT increased from Median PSADT increased from The third trial was a randomized, double-blinded , placebo controlled study published in Of the patients who enrolled, 64 patients were treated with placebo, 17 patients were treated with PJ, and patients were treated with pomegranate liquid extract, which contained the same compounds found in PJ, with the exception of a higher proportional content of pomegranate polyphenol and a lower anthocyanidin content.

The median change in PSADT was 4. The differences in results between the trials may be partly because of less aggressive disease in the patient population with lower starting PSA values, but they may also be because the first two trials lacked a placebo arm.

All three trials found that pomegranate extract was safe to consume. In light of these findings, researchers wondered if there may be a sensitive subpopulation that might benefit from PJ. One potential genetic biomarker candidate is manganese superoxide dismutase MnSOD , which is the primary antioxidant enzyme in mitochondria.

A polymorphism at codon 16 of the MnSOD gene in men encodes either alanine A or valine V. The AA genotype has been associated with more aggressive prostate cancer and with more sensitivity to antioxidants than the VA or VV genotype. In summary, the finding that men with the AA genotype who received pomegranate extract had greater lengthening of PSADT i.

In a study of prostate cancer patients reported in , the PJ intervention was well tolerated and no serious adverse effects were observed. In a pilot study reported in , the safety of PJ in patients with erectile dysfunction was examined.

No serious adverse effects were observed during this study, and no participant dropped out due to adverse side effects. In the analysis of the results, no statistical comparisons were made of the adverse side effects observed in the intervention arm and the placebo arm.

Selenium is an essential trace mineral involved in a number of biological processes, including enzyme regulation, gene expression, and immune function. Selenium was discovered in and named after the Greek goddess of the moon, Selene.

Food sources of selenium include meat, vegetables, and nuts. The selenium content of the soil where food is raised determines the amount of selenium found in plants and animals. For adults, the recommended daily allowance for selenium is 55 µg. Selenium is a component of the enzyme glutathione peroxidase, an enzyme that functions as an antioxidant.

Selenium is implicated in a number of disease states. Selenium deficiency may result in Keshan disease, a form of childhood cardiomyopathy, and Kaskin-Beck disease, a bone disorder. Selenium may also play a role in cancer. Animal and epidemiological studies have suggested there may be an inverse relationship between selenium supplementation and cancer risk.

The results indicated that selenium supplementation did not affect risk of skin cancer, although incidences of lung , colorectal , and prostate cancer were significantly reduced. There is evidence that selenoproteins may be associated with carcinogenesis.

For example, reduced expression of glutathione peroxidase 3 and SEPP have been observed in some tumors , while increased expression of glutathione peroxidase 2 occurs in colorectal and lung tumors.

Some companies distribute selenium as a dietary supplement. The FDA has not approved the use of selenium as a treatment or prevention for cancer. Different selenium-containing compounds have variable effects on prostate cancer cells as well as normal cells and tissues. Both naturally occurring and synthetic organic forms of selenium have been shown to decrease the growth and function of prostate cancer cells.

Studies have suggested that selenium nanoparticles may be less toxic to normal tissues than are other selenium compounds.

One study investigated the effects of selenium nanoparticles on prostate cancer cells. The treated cells had decreased activity of the androgen receptor , which led to apoptosis and growth inhibition. In a study, prostate cancer cells treated with sodium selenite a natural form of selenium exhibited increased levels of p53 a tumor suppressor.

Findings also revealed that p53 may play a key role in selenium-induced apoptosis. In a second study, the hormone-sensitive prostate cancer cell line LNCaP was modified to separately overexpress each of four antioxidant enzymes. Cells from the modified cell line were then treated with sodium selenite.

The cells overexpressing manganese superoxide dismutase MnSOD were the only ones able to suppress selenite-induced apoptosis.

These findings suggest that superoxide production in mitochondria may be important in selenium-induced apoptosis occurring in prostate cancer cells and that levels of MnSOD in cancer cells may determine the effectiveness of selenium in inhibiting those cells. One study treated prostate cancer cells and benign prostatic hyperplasia BPH cells with sodium selenite.

Growth of LNCaP cells was stimulated by noncytotoxic, low concentrations of sodium selenite; while growth inhibition occurred in hormone-insensitive PC-3 cells at these concentrations—prompting the authors to suggest that selenium may be beneficial in advanced prostate cancer—selenium supplementation may have adverse effects in hormone-sensitive prostate cancer.

adult male serum selenium concentrations are about 0. A study investigated whether various forms of selenium i. Elderly dogs received nutritionally adequate or supranutritional levels of selenium in the form of SeMet or Se-yeast.

Both types of selenium supplementation increased selenium levels in toenails and prostate tissue to a similar degree. The different forms of selenium supplementation showed no significant differences in DNA damage, proliferation, or apoptosis in the prostate.

At least one study has compared these three forms of selenium in athymic nude mice injected with human prostate cancer cells and found that MSeA was more effective in inhibiting tumor growth than was SeMet or selenite.

Mice were fed selenium-depleted or selenium-containing at nutritional or supranutritional levels diets for 6 months or 4 weeks and were then injected with PC-3 prostate cancer cells. Adult mice that were fed selenium-containing diets exhibited fewer tumors than did adult mice fed selenium-depleted diets.

In adult mice, selenium-depleted diets resulted in tumors with more necrosis and inflammation compared with selenium-containing diets. However, in young mice, tumor development and histopathology were not affected by dietary selenium. The effects of MSeA and methylselenocysteine MSeC have also been explored in a transgenic model of in situ murine prostate cancer development, the transgenic adenocarcinoma of the mouse prostate TRAMP mouse.

MSeA treatment also increased survival time of TRAMP mice. TRAMP mice that received MSeA treatment starting at age 10 weeks exhibited less aggressive prostate cancer than did mice that started treatment at 16 weeks, suggesting early intervention with MSeA may be more effective than later treatment.

The same research group later investigated some of the cellular mechanisms responsible for the different effects of MSeA and MSeC. MSeA and MSeC were shown to affect proteins involved in different cellular pathways.

MSeA mainly affected proteins related to prostate differentiation , androgen receptor signaling, protein folding, and endoplasmic reticulum-stress responses, whereas MSeC affected enzymes involved in phase II detoxification or cytoprotection.

The results of epidemiological studies suggest some complexity in the association between the blood levels of selenium and the risk of acquiring prostate cancer. As part of the European Prospective Investigation into Cancer and Nutrition EPIC -Heidelberg study, men completed dietary questionnaires, had blood samples taken, and were monitored every 2 to 3 years for up to 10 years.

The findings revealed a significantly decreased risk of prostate cancer for individuals with higher blood selenium concentrations.

Various molecular pathways have been explored to better understand the association between blood selenium levels and the development of prostate cancer. In the EPIC-Heidelberg study, polymorphisms in the selenium-containing enzymes GPX1 and SEP15 genes were found to be associated with prostate cancer risk.

Among SNPs analyzed, only GPX1 rs was related to overall prostate cancer risk. A retrospective analysis of prostate cancer patients and healthy controls showed an association between aggressive prostate cancer and decreased selenium and SEPP status.

Two SNPs were significantly associated with prostate cancer incidence: rs was associated with increased risk, and rs was associated with decreased risk.

Tumor SEPP1 mRNA expression levels were lower in men with lethal prostate cancer than in men with nonlethal prostate cancer. For men with the alanine-alanine AA genotype , higher selenium levels were associated with a reduced risk of presenting with aggressive disease, whereas the opposite was seen among men with a valine V allele.

An analysis of 4, men in the Health Professionals Follow-Up Study who were initially diagnosed with prostate cancer found that selenium supplementation of μg or more per day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality.

The authors recommended caution in the use of selenium supplements among men with prostate cancer. Risk of prostate cancer mortality rose at all levels of selenium consumption.

The authors reported no statistically significant association between selenium supplement use and biochemical recurrence , cardiovascular disease mortality, or overall mortality. In summary, these epidemiological studies present a conflicting picture.

Some studies showed that higher selenium levels were associated with a decreased risk of prostate cancer; others showed a correlation between higher selenium levels and more aggressive prostate cancer. Genetic differences in the SEPP gene may explain the different responses to selenium.

Interventional studies have examined the efficacy of selenium in preventing and treating prostate cancer. In one study, 60 healthy adult males were randomly assigned to receive either a daily placebo or µg of selenium glycinate supplements for 6 weeks.

Blood samples were collected at the start and end of the study. Compared with the placebo group, men who received selenium supplements had significantly increased activities of two blood selenium enzymes and significantly decreased levels of prostate-specific antigen PSA at the end of the study.

A meta-analysis published in reviewed human studies that investigated links between selenium intake, selenium status, and prostate cancer risk. However, in , results of a phase III randomized, placebo-controlled trial were reported. The trial investigated the effect of selenium supplementation on prostate cancer incidence in men at high risk for the disease.

The participants were monitored every 6 months for up to 5 years. Compared with placebo, selenium supplementation had no effect on prostate cancer incidence or PSA velocity.

The results also suggested that selenium supplementation had no effect on prostate cancer risk. A Cochrane review that examined the role of selenium in cancer prevention consolidated these studies in a meta-analysis and noted a risk ratio of 1.

SELECT was a phase III, randomized, double-blind , placebo-controlled, population-based trial. The primary endpoint of the clinical trial was incidence of prostate cancer. Initial results of SELECT were published in There were no statistically significant differences in rates of prostate cancer in the four groups.

On the basis of those findings, the data and safety monitoring committee recommended that participants stop taking the study supplements. Updated results of SELECT were published in The incidence of prostate cancer was also higher in men who took selenium than in men who took placebo, but the differences were not statistically significant.

A number of explanations have been suggested, including the dose and form of vitamin E used in the trial and the specific form of selenium chosen for the study. L-selenomethionine was used in SELECT, while selenite and Se-yeast had been used in previous studies.

SELECT researchers chose selenomethionine because it was the major component of Se-yeast and because selenite was not absorbed well by the body, resulting in lower selenium stores.

Toenail selenium concentrations were examined in two-case cohort subset studies of SELECT participants. Total selenium concentration in the absence of supplementation was not associated with prostate cancer risk. The authors concluded that men should avoid selenium supplementation at doses exceeding recommended dietary intakes.

Complicating this picture, an international collaboration compiled and reanalyzed data from 15 studies, including the SELECT trial, that investigated the association between blood and toenail selenium concentrations and prostate cancer risk.

Toenail selenium concentration was inversely associated with risk of total prostate cancer odds ratio , 0. In summary, data from the SELECT trial did not provide evidence that selenium, when given to unselected populations, decreased the risk of prostate cancer.

Subsequent analyses have shown that baseline selenium levels may influence the outcomes of selenium supplementation, though the evidence remains conflicting. Emerging evidence suggests that SNPs in genes related to both selenium and prostate cancer likely modify the effect of selenium supplementation.

Further research is needed to better understand which patients may benefit from or be harmed by selenium supplementation. To date, the most recent literature demonstrates that when administered to a non-selected population, selenium has no significant effect on either prostate cancer prevention or PSA levels.

A study explored the potential role of selenium in prostate cancer patients on active surveillance. Selenium was given in the form of Se-yeast. The results showed no significant difference in PSA velocity across treatment groups.

Concerningly, men who received high-dose selenium and had the highest baseline plasma selenium levels, had a higher PSA velocity than did men in the placebo group. There was no significant effect of selenium supplements on PSA velocity in men who had lower baseline levels of selenium.

Another study examined the potential role selenium played in the adjuvant setting. Prostate cancer patients were randomly assigned to receive either combination silymarin mg and selenomethionine µg supplement or placebo daily for 6 months following radical prostatectomy.

While there was no change in PSA levels between the groups after 6 months, the participants who received supplements reported improved quality of life and showed decreases in low-density lipoprotein cholesterol and total cholesterol.

Selenium supplementation was well tolerated in many clinical trials. In two published trials, there were no differences reported in adverse effects between placebo or treatment groups.

Soybean, a major food source and a medicinal substance, has been used in China for centuries. Soybean was used as one of the early food sources in China. Although records of soy use in China date back to the 11th century BCE, it was not until the 18th century that the soy plant reached Europe and the United States.

The soybean is an incredibly versatile plant. It can be processed into a variety of products including soy milk, miso, tofu, soy flour, and soy oil. Soy foods contain a number of phytochemicals that may have health benefits, but isoflavones have garnered the most attention.

Among the isoflavones found in soybeans, genistein is the most abundant and may have the most biological activity. Isoflavones are quickly taken up by the gut and can be detected in plasma as soon as 30 minutes after the consumption of soy products.

Studies suggest that maximum levels of isoflavone plasma concentration may be achieved by 6 hours after soy product consumption. Prostate tissue is known to express estrogen receptor beta and it has been shown that the isoflavone genistein has greater affinity for estrogen receptor beta than for estrogen receptor alpha.

A link between isoflavones and prostate cancer was first observed in epidemiological studies that demonstrated a lower risk of prostate cancer in populations consuming considerable amounts of dietary soy.

These early studies have led to a few clinical trials in humans using soy food products or supplements that targeted men with varying stages of prostate cancer. Although these studies showed modulation of intermediate endpoints or surrogate biomarkers of prostate cancer progression, the results indicating beneficial effects from soy or soy products have been mixed.

Several companies distribute soy as a dietary supplement. The FDA has not approved the use of soy as a treatment for cancer or any other medical condition. A number of laboratory studies have examined ways in which soy components affect prostate cancer cells.

In one study, human prostate cancer cells and normal prostate epithelial cells were treated with either an ethanol vehicle carrier or isoflavones.

Treatment with genistein decreased COX-2 mRNA and protein levels in cancer cells and normal epithelial cells more than did treatment with the vehicle. In addition, cells treated with genistein exhibited reduced secretion of prostaglandin E2 PGE2 and reduced mRNA levels of the prostaglandin receptors EP4 and FP, suggesting that genistein may exert chemopreventive effects by inhibiting the synthesis of prostaglandins, which promote inflammation.

The isoflavones were shown to down regulate growth factors involved in angiogenesis e. These findings suggest that genistein and daidzein may have chemopreventive properties.

However, during the 72 hours of incubation , only genistein provoked effects on the dynamic phenotype and decreased invasiveness in PC-3 cells. These results imply that invasive activity is at least partially dependent on membrane fluidity and that genistein may exert its antimetastatic effects by changing the mechanical properties of prostate cancer cells.

No such effects were observed for daidzein at the same dose. Some experiments have compared the effects of individual isoflavones with isoflavone combinations on prostate cancer cells. In one study, human prostate cancer cells were treated with a soy extract containing genistin, daidzein, and glycitin , genistein, or daidzein.

The soy extract induced cell cycle arrest and apoptosis in prostate cancer cells to a greater degree than did treatment with the individual isoflavones. Genistein and daidzein activated apoptosis in noncancerous benign prostatic hyperplasia BPH cells, but the soy extract had no effect on those cells.

These findings suggested that products containing a combination of active compounds e. All of the treatments resulted in decreased cell proliferation, but the greatest reductions occurred using the combination of genistein, biochanin A, and quercetin.

The triple combination treatment induced more apoptosis in prostate cancer cells than did individual or doublet compound treatments.

These results indicate that combining phytoestrogens may increase the effectiveness of the individual compounds. At least one study has examined the combined effect of soy isoflavones and curcumin. Human prostate cancer cells were treated with isoflavones, curcumin, or a combination of the two.

Curcumin and isoflavones in combination were more effective in lowering PSA levels and expression of the androgen receptor than were curcumin or the isoflavones individually.

Animal models of prostate cancer have been used in studies investigating the effects of soy and isoflavones on the disease. The TRAMP mice fed with genistein exhibited reduced cell proliferation in the prostate compared with TRAMP mice fed a control diet.

The genistein-supplemented diet also reduced levels of ERK-1 and ERK-2 proteins important in stimulating cell proliferation as well as the growth factor receptors epidermal growth factor receptor EGFR and insulin like growth factor-1 receptor IGF-1R in TRAMP mice, suggesting that down regulation of these proteins may be one mechanism by which genistein exerts chemopreventive effects.

Mice fed low-dose genistein exhibited more cancer cell metastasis and greater osteopontin expression than mice fed the control or the high-dose genistein diet.

These results indicate that timing and dose of genistein treatment may affect prostate cancer outcomes and that genistein may exert biphasic control over prostate cancer. Mice that were fed genistein exhibited less cancer cell metastasis but no change in primary tumor volume, compared with mice fed a control diet.

Furthermore, other data suggested that genistein inhibits metastasis by impairing cancer cell detachment. In contrast, in a study reported in , there were more metastases in secondary organs in genistein-treated mice than in vehicle-treated mice.

In addition, there was a reduction in tumor cell apoptosis in the genistein-treated mice compared with the vehicle-treated mice. These findings suggest that genistein may stimulate metastasis in an animal model of advanced prostate cancer.

Radiation therapy is commonly used in prostate cancer, but, despite this treatment, disease recurrence is common. Therefore, combining radiation with additional therapies may provide longer-lasting results. Cells that were treated with both isoflavones and radiation exhibited greater decreases in cell survival and greater expression of proapoptotic molecules than cells treated with isoflavones or radiation only.

Nude mice were implanted with prostate cancer cells and treated by gavage with genistein Mixed isoflavones were more effective than genistein in inhibiting prostate tumor growth, and combining isoflavones with radiation resulted in the largest inhibition of tumor growth.

In addition, mice given soy isoflavones in combination with radiation did not exhibit lymph node metastasis, which was seen previously in other experiments combining genistein with radiation.

These preclinical findings suggest that mixed isoflavones may increase the efficacy of radiation therapy for prostate cancer.

In the treatment of prostate cancer, bone health is a common concern in the setting of hormone deprivation therapy, which is associated with bone loss. Because of increased beta versus alpha estrogen receptor binding, soy-derived compounds are thought to be protective of bone.

Animal studies have shown that genistein and daidzein can prevent or reduce bone loss in a manner similar to synthetic estrogen. Both isoflavones may modulate bone remodeling by targeting and regulating gene expression and may inhibit calcium urine excretion, which also helps to maintain bone density.

Human studies evaluating isoflavones and soy for the prevention and treatment of prostate cancer have included epidemiological studies and early-phase trials. Several phase I-II randomized clinical studies have examined isoflavones and soy product for bioavailability , safety, and effectiveness in prostate cancer prevention or treatment.

Journal home All issues About the journal. Jinyao CHEN , Yang SONG , Lishi ZHANG Author information. Jinyao CHEN West China School of Public Health, Sichuan University Yang SONG West China School of Public Health, Sichuan University Lishi ZHANG West China School of Public Health, Sichuan University.

Corresponding author. Keywords: lycopene , tomato , prostate cancer , meta-analysis , systematic review. JOURNAL FREE ACCESS. Published: Received: October 18, Released on J-STAGE: July 25, Accepted: - Advance online publication: - Revised: -.

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