Consumption Of Isoflavones Research Articles

Update on genistein and thyroid: an overall message of safety

Genistein aglycone, one of the soy isoflavones, has been reported to be beneficial in the treatment of menopausal vasomotor symptoms, osteoporosis, and cardiovascular diseases, as well as in a variety of cancers. However, issues of potential harm on thyroid function resulting from soy isoflavones consumption have been raised. Much of the evidence for the goitrogenic effects of isoflavones is derived from experimental in vitro and in vivo studies. Goitrogenic effects were also noted in infants fed non-iodine-fortified, soy-based formula, a problem that was easily solved with iodine fortification. Recent studies suggest that genistein shows a good profile of safety on the thyroid although definitive conclusions have not reached. The aim of this brief review is to summarize and better clarify the effects of genistein on human thyroid health.

Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women

Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.

Soy Isoflavones and Cardiovascular Disease Epidemiological, Clinical and -Omics Perspectives

Cardiovascular disease (CVD) mortality rates are lower in Asian countries where dietary patterns are very different from Western diet. A number of studies have linked these lower rates to the inclusion of soy products as a staple food in those countries. Soy is the richest dietary source of isoflavones, a type of phytoestrogen associated with many potentially beneficial effects. Isoflavone-containing soy protein consumption has been linked to reduced levels of LDL cholesterol in hypercholesterolemic patients. This effect is increased with the concomitant administration of isoflavones, and seems to be also complemented by the isoflavone capacity to restore the endothelial function in patients with weak and moderated endothelial dysfunction. The effects are variable depending on individuals� � � metabolism and in particular to their ability to convert daidzein to equol that seems to be restricted to approximately 1/3 of the population. Equol production has been indeed linked to a decreased arterial stiffness and antiatherosclerotic effects via NO production. Because the relevance of isoflavones consumption on the modulation of cardiovascular risk still remains unclear, this paper aims to review the existing knowledge on the biological activity of the isoflavones on the human cardiovascular system from an epidemiological, clinical and -omics point of view.

Isoflavonas de soya y salud humana: cáncer de mama y sincronización de la pubertad

Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

Genistein as a Potential Anticancer Agent against Ovarian Cancer

Genistein is known as the major component of isoflavone, which is present in high-soy diets. Genistein has received much attention because of its chemopreventive and therapeutic effects on various types of cancers. Numerous studies have shown that genistein has antineoplastic effects against ovarian cancer. Several epidemiological studies have shown that women who have high consumption of isoflavones have a relatively low incidence of ovarian cancer. Genistein inhibits ovarian carcinogenesis by pleiotropic mechanisms. A higher affinity to estrogen receptor β is one probable explanation for its ability to reduce the risk of ovarian cancer. Genistein also targets multiple cellular signal transduction pathways associated with cell cycle regulation and apoptosis. In addition, genistein has been suggested to have antiangiogenic and antioxidant activities. Herein, we summarize recent results from epidemiological and experimental studies to identify the role of genistein in ovarian cancer. Further studies are needed to achieve conclusive results and determine the clinical applications of genistein.

Study on Soy Isoflavone Consumption and Risk of Breast Cancer and Survival

Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.

Soya isoflavone consumption in relation to carotid intima–media thickness in Chinese equol excretors aged 40–65 years

Previous studies have suggested that the daidzein metabolite equol rather than daidzein itself contributes to the beneficial effect of soya foods in the prevention of CVD. The aim of the present study is to examine the proportion of equol excretion in Chinese adults and compare plasma lipids and carotid artery intima-media thickness (IMT) between equol excretors and non-excretors, and to evaluate the effect of soya isoflavone intakes on serum lipids and IMT in either equol excretors or non-excretors. Subjects (n 572; women n 362, men n 210) were recruited for the present study. An overnight urine sample was provided by each subject on their usual diet to quantify urinary concentrations of daidzein and equol. Far-wall IMT was determined by B-mode ultrasound in the right carotid at two sites, carotid bulb (CB-IMT) and common carotid artery (CCA-IMT), and fasting serum lipids were measured. Habitual dietary intakes were estimated with a FFQ, and soya isoflavone intake derived from the FFQ was assessed. Of the 572 subjects, the proportion of equol excretors on their usual diet was 25·0 % (n 143). Compared with non-excretors, equol excretors showed significantly lower serum TAG (-38·2 (95 % CI -70·4, -5·9) %, P = 0·012) and CCA-IMT (-4·9 (95 % CI -9·7, -0·3) %, P = 0·033). Equol excretors with higher daily isoflavone intakes (-5·4 mg/d) had significantly lower IMT (-16·2 %, P = 0·035) and tended to have higher HDL-cholesterol (P = 0·055) than did those with lower daily isoflavone intakes (1·5 mg/d), while no association was observed between soya isoflavone intakes and serum lipids or IMT in non-excretors. In conclusion, the benefits of soya isoflavones in preventing CVD may be apparent among equol excretors only.

2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: Vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition

Isoflavone consumption correlates with reduced rates of cardiovascular disease. Epidemiological studies and clinical data provide evidence that isoflavone metabolites, such as the isoflavan equol, contribute to these beneficial effects. In this study we developed a new route to isoflavans and isoflavenes via 2-morpholinoisoflavenes derived from a condensation reaction of phenylacetaldehydes, salicylaldehydes and morpholine. We report the synthesis of the isoflavans equol and deoxygenated analogues, and the isoflavenes 7,4′-dihydroxyisoflav-3-ene (phenoxodiol, haganin E) and 7,4′-dihydroxyisoflav-2-ene (isophenoxodiol). Vascular pharmacology studies reveal that all oxygenated isoflavans and isoflavenes can attenuate phenylephrine-induced vasoconstriction, which was unaffected by the estrogen receptor antagonist ICI 182,780. Furthermore, the compounds inhibited U46619 (a thromboxane A2 analogue) induced vasoconstriction in endothelium-denuded rat aortae, and reduced the formation of GTP RhoA, with the effects being greatest for equol and phenoxodiol. Ligand displacement studies of rat uterine cytosol estrogen receptor revealed the compounds to be generally weak binders. These data are consistent with the vasorelaxation activity of equol and phenoxodiol deriving at least in part by inhibition of the RhoA/Rho-kinase pathway, and along with the limited estrogen receptor affinity supports a role for equol and phenoxodiol as useful agents for maintaining cardiovascular function with limited estrogenic effects.

Dietary Isoflavone Absorption, Excretion, and Metabolism in Captive Cheetahs (Acinonyx jubatus)

Dietary isoflavones, capable of influencing reproductive parameters in domestic cats (Felis catus), have been detected in commercial diets fed to captive cheetahs (Acinonyx jubatus). However, the absorptive and metabolic capacity of cheetahs towards isoflavones has not yet been studied. Experiments were designed to describe the plasma concentration-time curve, metabolite profile, and urinary and fecal excretion of genistein and daidzein in cheetahs following consumption of isoflavones. Four adult cheetahs were administered a single oral bolus of genistein and daidzein, and five juvenile cheetahs consuming a milk replacer formula found to contain isoflavones were also included. Urine was collected from all animals, and blood and feces were also collected from adult cheetahs following isoflavone exposure. Samples were analyzed for isoflavone metabolite concentration by liquid chromatography-electrospray ionization-multiple reaction ion monitoring mass spectrometry and high-performance liquid chromatography. Sulfate conjugates were the primary metabolites detected of both genistein and daidzein (60-80% of total isoflavones present) in the plasma and urine of cheetahs. A smaller proportion of daidzein was detected as conjugates in the urine of juvenile cheetahs, compared to adult cheetahs. Other metabolites included unconjugated genistein and daidzein, O-desmethylangolensin, and dihydrodaidzein, but not equol. Only 33% of the ingested genistein dose, and 9% of daidzein, was detected in plasma from adult cheetahs. However, of the ingested dose, 67% of genistein and 45% of daidzein were detected in the feces of adults. This study revealed that cheetahs appear efficient in their conjugation of absorbed dietary isoflavones and only a small fraction of ingested dose is absorbed. However, the capacity of the cheetah to conjugate genistein and daidzein with sulfate moieties appears lower than reported in the domestic cat. This may confer greater opportunity for biologic activity of isoflavones in the cheetah than would be predicted from findings in the domestic cat. However, further investigation is required.

Effect of a soy isoflavone intervention on estrogen-related gene expression in the healthy high risk breast.

635 Background: Soy isoflavone consumption may reduce breast cancer risk, and should cause measureable changes in gene expression in the breast. We conducted a Phase IIB trial of soy intervention (1:1 randomization to G- 2535or placebo) and studied effects on the expression of a 28- gene panel, and other biomarkers. Methods: Breast sampling was performed using random fine needle aspiration; cDNA was prepared from 100 ng of purified RNA and amplified. We selected 30 genes: 14 targets of genistein, 9 related to ERα, 5 associated with epithelial atypia, and 2 housekeeping (HSK) genes (GAPDH and HPRT1). Taqman low density arrays (TLDA) were used to perform quantitative PCR reactions. The mean Ct values of triplicates were normalized against HSK and month-6 minus baseline differences were t-tested. ANOVA was used for global comparisons between groups. Results: RNA analyses could be performed on 89 of 98 women (9 had insufficient RNA). The soy group showed increased expression of 18/28 genes post-intervention; Benjamini-Hochberg adjustment reduced this number to 14 genes. These included 7 related to genistein effect (BCL-2, CDKN1A, CDKN2A, DDIT3, FAS, PARP-1, and TP53), 5 related to estrogen response (ESR1, FOXA1, MYB, PGR, SCUBE2) and 2 related to breast atypia (AR and Wnt5B). The control group showed increased expression of 8 genes, but after adjustment, one (IGF-1) remained significant. On comparing the change in gene expression between the soy and control groups, there were significant increases in 4 genes: FAS, FGFR3, FOXA1, MYB, which were non-significant after adjustment. The mean change across all 28 genes in the soy group from baseline to 6-months was 1.56-fold, whereas for control subjects it was 1.25-fold (p=0.02). At 6-months, gene expression in the soy group was 1.66-fold that of HSK, compared to 1.31 for the control subjects (p=0.0001). Conclusions: We saw significant increases in soy-induced genes in the breast following a 6-month intervention suggest an estrogenic effect on the breast. However, spontaneous variation in gene expression resulted in statistically non-significant change between groups. The reproducibility of expression of specific genes needs to be considered in design of future studies.

Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma

Epidemiologic studies have associated higher dietary consumption of soy isoflavones with decreased self-report of cough and allergic respiratory symptoms, but the pharmacodynamic effects of soy isoflavone on asthmatic model have not been well-described. Here, we hypothesized that soy isoflavone may have potential effects on airway hyperresponsiveness, inflammation and airway remodeling in a murine of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts, and for cytokine levels. Lung tissues were examined for cell infiltration, mucus hypersecretion and airway remodeling, and for the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Oral administration of soy isoflavone significantly reduced ovalbumin-induced airway hyperresponsiveness to intravenous methacholine, and inhibited ovalbumin-induced increases in eosinophil counts. RT-PCR analysis of whole lung lysates revealed that soy isoflavone markedly suppressed ovalbumin-induced mRNA expression of eotaxin, interleukin(IL)-5, IL-4 and matrix metalloproteinase-9, and increased mRNA expression of interferon (IFN)-γ and tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. Soy isoflavone also substantially recovered IFN-γ/IL-4 (Th1/Th2) levels in bronchoalveolar lavage fluid. In addition, histologic studies showed that soy isoflavone dramatically inhibited ovalbumin-induced lung tissue eosinophil infiltration, airway mucus production and collagen deposition in lung tissues. Our findings suggest that soy isoflavone as nutritional supplement may provide a novel means for the treatment of airway inflammatory disease.

Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study

Isoflavone intake has been associated with a reduction in the risk of cardiovascular disease in postmenopausal women. The aim of the present study was to determine if the effects of isoflavones on vascular function differ between premenopausal and postmenopausal women and between women who smoke and those who do not. Women smokers and nonsmokers who consumed 50mg of isoflavone/day as black soybean tea for a period of 2months (n=55, mean age 39) were enrolled in the present study. We examined endothelial function, which was assessed by the percent change in flow-mediated dilation (%FMD) and arterial wall stiffness using the cardio-ankle vascular index (CAVI), as well as by biochemical parameters of the blood. Neither premenopausal (p=0.697) nor postmenopausal (p=0.389) smokers experienced an increase in %FMD after daily consumption of isoflavones. However, both premenopausal (p=0.004) and postmenopausal (p=0.019) nonsmokers exhibited a marked elevation in %FMD. By contrast, isoflavone intake effectively reduced CAVI among both premenopausal smokers (p=0.027) and nonsmokers (p=0.013), but had no effect on CAVI among postmenopausal smokers (p=0.169) or nonsmokers (p=0.128). The women smokers and nonsmokers did not differ in age or %FMD at the time of enrollment in the study. Thus, isoflavones have different effects on vascular endothelial function and arterial wall stiffness in premenopausal and postmenopausal smokers and nonsmokers.

Development of Bioluminescent Enzyme Immunoassay for S-Equol Using Firefly Luciferase and Its Application to the Assessment of Equol-Producer Status

In this study, we developed a specific bioluminescent enzyme immunoassay (BLEIA) for S-equol, employing firefly luciferase as a labeling enzyme, as an alternative to HPLC methods. Satisfactory correlation (r=0.992) was shown when this S-equol BLEIA was compared with HPLC. The cross-reactivity with R-equol as its diastereoisomer is <5%, and that with daidzein, which is the substrate of equol, is 0.02%. Frequencies of Japanese equol producers determined using two distinct approaches were compared: a threshold value for urinary S-equol concentration of 232 ng/ml gave frequencies of 32% of men and 19% of women. These values correspond to the results for log(10)-transformed urinary S-equol to daidzein ratio threshold of -1.75, namely, 34% of men and 19% of women. When the changes in concentration of urinary equol and daidzein were measured after ingestion of isoflavone, the maximum concentration (C(max)) of urinary equol appeared after 9.6 h of isoflavone consumption; this C(max) was 2 h later than that for daidzein. The S-equol BLEIA documented in this study is expected to be an important tool for the assessment of equol producer status and demonstration of the bioavailability of isoflavone.

Abstract P6-14-13: A Flavone from Traditional East Asian Natural Extract Inhibits STAT3 and Tumor Growth in a Syngeneic Mouse Breast Cancer Model

Abstract Background: Recent studies have shown that increased dietary consumption of flavones and isoflavones is associated with reduced risk of developing cancer. Natural plants/herbs used in Traditional East Asian Medicine (TEAM) have been recognized as potentially efficacious natural treatments against cancer and are enriched with isoflavones and flavones, as well as other interesting compounds. We used a novel high throughput screening method to identify natural extracts that may have a potential anti-cancer effect and identified the TEAM natural product Scutellaria baicalensis and a known active component, the flavone, baicalein. The objective of our current study is to investigate the anti-cancer effects of baicalein in vitro and in vivo. Methods: In vitro testing was performed in mouse (C3L5) and human (SKBR3) breast cancer cell lines. Cell viability was assessed by MTT assay. Apoptosis was assessed using FITC-Annexin V and PI staining with bivariate reading by flow cytometry at 48 h. A syngeneic mouse breast cancer model (C3H/HeJ — C3L5) was used for in vivo testing. Mice bearing subcutaneous tumors were either treated with daily intraperitoneal injection of vehicle or baicalein (20 mg/kg) five days a week for three weeks (n=6/group). Tumor size and weights were measured. Results: Baicalein had a marked cytotoxic effect in C3L5 cells with an IC50 of less than 10mM (data not shown). FITC-Annexin V and PI analysis with flow cytometry for C3L5 cells treated at 10μM for 48h showed a marked increase in the Annexin V positive fraction indicative of apoptosis. In vivo studies demonstrated a significantly decreased tumor growth in mice treated with intraperitoneal baicalein when compared to the control group (P&amp;lt;0.05). Baicalein treated cells demonstrated STAT3 inhibition on western blot analysis by decreased presence of phospho-STAT3 (data not shown). Conclusions: Baicalein, a flavone from TEAM demonstrates significant anti-cancer effects due to apoptosis in breast cancer. STAT3, a well-known anti-apoptotic signaling intermediate, is inhibited in activation as reflected by decreased phosphoSTAT3 which may account for these effects. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-13.

Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies

Numbers of epidemiologic studies assessing soy consumption and risk of breast cancer have yielded inconsistent results. We aimed to examine the association between soy isoflavones consumption and risk of breast cancer incidence or recurrence, by conducting a meta-analysis of prospective studies. We searched for all relevant studies with a prospective design indexed in PUBMED through September 1st, 2010. Summary relative risks (RR) were calculated using fixed- or random-effects models. Pre-specified stratified analyses and dose-response analysis were also performed. We identified 4 studies of breast cancer recurrence and 14 studies of breast cancer incidence. Soy isoflavones consumption was inversely associated with risk of breast cancer incidence (RR = 0.89, 95% CI: 0.79-0.99). However, the protective effect of soy was only observed among studies conducted in Asian populations (RR = 0.76, 95% CI: 0.65-0.86) but not in Western populations (RR = 0.97, 95% CI: 0.87-1.06). Soy isoflavones intake was also inversely associated with risk of breast cancer recurrence (RR = 0.84, 95% CI: 0.70-0.99). Stratified analyses suggested that menopausal status may be an important effect modifier in these associations. We failed to identify a dose-response relationship between total isoflavones intake and risk of breast cancer incidence. Our study suggests soy isoflavones intake is associated with a significant reduced risk of breast cancer incidence in Asian populations, but not in Western populations. Further studies are warranted to confirm the finding of an inverse association of soy consumption with risk of breast cancer recurrence.

Plasma testosterone and sex hormone‐binding globulin concentrations and the risk of prostate cancer among Japanese men: A nested case‐control study

Sex hormones, particularly androgens, have been implicated in prostate carcinogenesis. Overall, however, prospective studies have reported no association between circulating levels of sex hormones and the risk of prostate cancer. However, despite the possible difference in the effects of hormones on prostate cancer risk by stage, age, body mass index (BMI) and isoflavones, evidence for these is sparse. Moreover, few studies have been conducted in Asian populations, who are relatively lean and have high isoflavone consumption. We examined the hypothesis that plasma concentrations of circulating testosterone and sex hormone-binding globulin (SHBG) are associated with the risk of prostate cancer in a case-control study nested in the Japan Public Health Center-based Prospective Study. Concentrations of total testosterone and SHBG were measured in plasma samples from 201 patients with prostate cancer and 402 matched control participants, and concentrations of free testosterone were calculated. No overall association between the plasma levels of any hormone and total prostate cancer was observed. Odds ratios (95% confidence interval [CI]) in the highest versus lowest group were 0.71 (95% CI = 0.36-1.41, Ptrend = 0.43) for total testosterone, 0.70 (95% CI = 0.39-1.27, Ptrend = 0.08) for free testosterone and 1.38 (95% CI = 0.69-2.77, Ptrend = 0.23) for SHBG. When stratified by cancer stage, age, BMI and plasma isoflavone level, free testosterone was inversely associated with localized cancers and equol producers, while SHBG was associated with an increased risk of prostate cancer in younger men. In conclusion, in this nested case-control study, concentrations of circulating total testosterone, free testosterone or SHBG were not strongly associated with a risk for total prostate cancer.

Prostate Cancer Working Group Report

The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.

Enhanced Mammary Progesterone Receptor-A Isoform Activity in the Promotion of Mammary Tumor Progression by Dietary Soy in Rats

Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-methyl-N-nitrosourea, dietary intake of soy protein isolate (SPI) reduced mammary tumor occurrence but increased incidence of more invasive tumors in tumored rats, relative to the control diet casein. Here we evaluated whether mammary tumor progression in tumor-bearing rats lifetime exposed to SPI is associated with deregulated progesterone receptor (PR) isoform expression. In histologically normal mammary glands of rats with invasive ductal carcinoma lesions, PR-A protein levels were higher for SPI- than casein-fed rats, whereas PR-B was undetectable for both groups. Increased mammary PR-A expression was associated with higher transforming growth factor-β1, stanniocalcin-1, and CD44 transcript levels; lower E-cadherin and estrogen receptor-α expression; and reduced apoptotic status in ductal epithelium. Serum progesterone (ng/ml) (CAS: 25.94 ± 3.81; SPI: 13.19 ± 2.32) and estradiol (pg/ml) (CAS: 27.9 ± 4.49; SPI: 68.48 ± 23.87) levels differed with diet. However, sera from rats of both diet groups displayed comparable mammosphere-forming efficiency in human MCF-7 cells. Thus, soy-rich diets may influence the development of more aggressive tumors by enhancing PR-A-dependent signaling in premalignant breast tissues.

Effect of daidzein on anxiety, social behavior and spatial learning in male Balb/cJ mice

Daidzein is an abundant isoflavone present in soy. It is unique as it can be further metabolized into equol, a compound with greater estrogenic activity than other isoflavones. The potential benefit of daidzein in the prevention of various cancers and cardiovascular diseases has drawn attention to this molecule and isoflavone consumption is increasing around the world. However, it remains unclear whether daidzein affects locomotor activity, anxiety, social behavior or spatial memory. Here we report the results from a range of tests designed to assess anxiety, social behavior and spatial learning and memory in male Balb/cJ mice following consumption of daidzein for 30 days. We found that daidzein treatment significantly increased locomotor activity in the open field, elevated plus-maze and Morris water-maze tests; resulted in increased amicable behavior, decreased aggression and decreased sexual behavior during social interaction tests; and resulted in an anxiolytic effect amongst treated males. We found no effect of daidzein consumption on the acquisition and retrieval of spatial memory. Our results suggest that long-term consumption of daidzein may produce significant effects on locomotor activity, mood and social behavior without significant effects on learning and memory.

Lifetime Dietary Exposure To Soy Isoflavones Is Beneficial To Prostate And Testicular Health In 100 Day‐Old Male Long‐Evans Rats

Consumption of soy isoflavones appears to be beneficial for several health parameters. We examined the effect of dietary exposure (from conception) of soy isoflavones on body weight (BW), white adipose tissue (WAT), prostate weight, and testicular weights (TW) and for several morphometric parameters. During pre‐ and postnatal development male rats were exposed to either a phytoestrogen‐rich (PR) or phytoestrogen‐low (PL) diet. At 100 days of age the male rats were sacrificed, tissues weighed, processed and analyzed by histology methods. BW and prostate/BW ratios were slightly decreased in the PR vs. PL groups (but were non‐significant). WAT/BW ratios were significantly less in the PR vs. the PL fed animals. Additionally, the percentage of invaginations of prostate glandular tissue was significantly greater in the PR vs. PL males. TW and TW/BW ratios were significantly greater in the PR vs. PL fed animals. Sertoli cell area was significantly greater in the PR vs. PL animals which accounted for greater seminiferous tubule lumens and seminiferous tubule areas in the PR vs. PL groups. These data indicate that consumption of a soy isoflavone rich diet appears to be beneficial in decreasing prostate glandular tissue and WAT deposition while increasing testicular weight, Sertoli cell area and seminiferous tubule volume which suggest a positive influence on reproductive capacity in males. (Grant Support: USDA 2004‐01811)