Dietary intake and major sources of plant lignans in Latvian men and women.

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) µg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Validation of FFQ-based assessment of dietary lignans compared with serum enterolactone in Swedish women.

The validity of using FFQ to assess dietary lignans is uncertain. We aimed to validate the use of FFQ for the assessment of dietary intake of lignans compared to the serum biomarker enterolactone, the main product of dietary lignans' metabolism in human subjects. A random sample of women, aged 55-75 years, from the Swedish Mammography Cohort was selected. Information from two FFQ, the FFQ-87 (sixty-seven food items) and the FFQ-97 (ninety-three food items), and blood samples were collected. Dietary intake of lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol and syringaresinol) was assessed by the FFQ. Serum concentrations of enterolactone were analysed by time-resolved fluoroimmunoassay. The correlation coefficient between energy-adjusted lignan intake and serum enterolactone was estimated in crude and multivariable-adjusted models, taking into account the factors potentially influencing the serum enterolactone. Among the 135 participants aged 55-75 years, with a mean BMI of 26·7 kg/m², the average energy-adjusted intake of total lignans was 1616 (sd 424) and 1516 (sd 409) µg/d according to the FFQ-87 (forty-five food items containing lignans) and the FFQ-97 (sixty-five food items containing lignans), respectively. The mean concentration of serum enterolactone was 23·2 (sd 15·4) nmol/l. The adjusted Pearson's correlation between dietary intake of lignans assessed by the FFQ-97 and serum enterolactone was statistically significant (r 0·22, P= 0·01). No significant correlation was observed for the FFQ-87 (r 0·09, P= 0·30). The present study indicates that the FFQ-97 might be better than the FFQ-87 for assessing dietary intake of lignans, although the correlation was low.

Alkylresorcinols in Latvian and Finnish breads.

The alkylresorcinol (AR) content and relative homologue composition were determined in 9 Latvian and 11 Finnish soft breads. ARs were extracted with hot 1-propanol and quantified, using a gas chromatography-mass spectrometry method. The total AR content (µg/g dry matter) varied from 560 to 840 in rye breads, from 500 to 700 in Finnish mixed rye and wheat flour breads, from 200 to 300 in Latvian mixed rye and wheat flour breads and from 25 to 30 in white wheat breads. Rye and white wheat breads in the two countries varied only slightly in AR content, but there were wide variations in AR content in mixed flour breads. The AR contents in soft breads could be indicators of bran or fibre content, but not of whole-grain flour content.

Synergistic effect of isoflavone glycosides and fructooligosaccharides on postgastrectomy osteopenia in rats.

Fructooligosaccharides stimulate the growth of Bifidobacteria, which cleave isoflavone glycosides to yield corresponding aglycones, and convert metabolites by enhancing enterohepatic recirculation of isoflavones in rats. In the present study, we determined the synergistic effect of dietary isoflavone glycosides and fructooligosaccharides on postgastrectomy osteopenia in rats. Nine-week-old male Sprague-Dawley rats were gastrectomized (n = 20) or sham operated, (control, n = 5) and then randomly assigned to 5 diet groups: sham-a purified diet control, gastrectomized-control, gastrectomized-isoflavone (0.2% isoflavone glycosides), gastrectomized-fructooligosaccharides (7.5% fructooligosaccharides), and isoflavone and fructooligosaccharides (0.2% isoflavone glycosides + 7.5% fructooligosaccharides). After 6 weeks, the rats were killed and biological samples were collected. In gastrectomized rats, fructooligosaccharides prevented femoral bone fragility, but isoflavone without fructooligosaccharides did not inhibit postgastrectomy osteopenia. Isoflavone and fructooligosaccharides exhibited a synergistic in the distal metaphyseal trabecular bone, indicated by peripheral quantitative computed tomography. Moreover, fructooligosaccharides increased calcium absorption and equol production from daidzein in gastrectomized rats. These results indicate that isoflavone alone did not inhibit postgastrectomy osteopenia, but the combination of isoflavone and fructooligosaccharides improved the inhibition of trabecular bone loss by increasing calcium absorption and equol production through fructooligosaccharides supplementation.

Comparative activities of the S-enantiomer and racemic forms of equol on bone fragility in ovariectomized mice.

We compared the effects of the S-enantiomer and racemic forms of equol on bone using ovariectomized (OVX) mice. Femoral bone mineral density and bone strength decreased in the OVX mice, but not in OVX mice administered 0.5 mg/d S-equol. This, however, did not hold for racemic equol. Serum and urine S-equol concentrations were higher in the mice administered S-equol than in those administered racemic equol. These results suggest that the inhibitory effects of S-equol on bone fragility in OVX mice are greater than those of racemic equol.

Transcriptional activity of estrogen-related receptor γ (ERRγ) is stimulated by the phytoestrogen equol.

Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor lacking identified natural ligands. The synthetic estrogen receptor ligands 4-hydroxytamoxifen and diethylstilbestrol have, however, been shown to bind to and abolish the constitutive transcriptional activity of ERRγ. Certain phytoestrogens were recently reported to act as agonists of the related ERRα. We investigated whether phytoestrogens also modulated the transcriptional activity of ERRγ. We analyzed a selection of phytoestrogens for their potential agonistic or antagonistic activity on ERRγ. In transiently transfected PC-3 and U2-OS cells equol stimulated the transcriptional activity of ERRγ and enhanced its interaction with the coactivator GRIP1. The agonistic effect of equol was abolished by 4-hydroxytamoxifen. Equol induced a conformational change in the ERRγ ligand-binding domain. Based on structural models of the ERRγ ligand-binding domain, we were able to introduce mutations that modulated the agonistic potential of equol. Finally, equol enhanced the growth inhibitory effect of ERRγ on the prostate cancer PC-3 cells. In conclusion, we have demonstrated that the phytoestrogen equol acts as an ERRγ agonist.

Dietary phytoestrogens and the risk of ovarian cancer in the women's lifestyle and health cohort study.

BACKGROUND: Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. METHODS: In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. RESULTS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. CONCLUSIONS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. IMPACT: Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies.

Relationship between animal protein intake and muscle mass index in healthy women.

The amount and the type of dietary protein could play a role in determining the quantity of skeletal muscle mass. The aim was to examine the relationship between the type of protein intake and the level of muscle mass in healthy omnivorous and vegetarian Caucasian women. The design of the present study was an observational and cross-sectional study. Twenty-one omnivores (Om) and nineteen vegetarians (Ve) were recruited. Muscle mass index (urinary creatinine), dietary intake (5 d dietary records) and biochemical analyses (hormone, phyto-oestrogen and lipid profiles) were obtained. We found differences between groups for muscle mass (Ve: 18 kg v. Om: 23 kg; P = 0.010), muscle mass index (Ve: 6.7 kg/m2 v. Om: 8.3 kg/m2; P = 0.002), animal protein intake in g/d (P = 0.001) and in g/kg body weight per d (P = 0.003), plant protein intake in g/d (P = 0.015) and in g/kg body weight per d (P = 0.007), the animal:plant protein intake ratio (P = 0.001) and sex hormone-binding globulin (SHBG) (P = 0.001). Muscle mass index still correlated with animal protein intake in g/d (P = 0.001) and in g/kg body weight per d (P = 0.008), and the animal:plant protein intake ratio (P = 0.007) even after controlling for SHBG and plant protein intake. Finally, animal protein intake (g/d) was the independent predictor of muscle mass index (adjusted r2 0.42). Thus, a vegetarian diet is associated with a lower muscle mass index than is an omnivorous diet at the same protein intake. A good indicator of muscle mass index in women seems to be animal protein intake.

The protective association of high plasma enterolactone with breast cancer is reasonably robust in women with polymorphisms in the estrogen receptor alpha and beta genes.

It is plausible that polymorphisms in the estrogen receptor alpha and beta genes (ESR1 and ESR2) may modulate the association between enterolactone and breast cancer. Seven polymorphisms in ESR1 (rs827422, rs1709184, rs2347867, rs3020328, rs72207, rs2982896, and rs2234693) and 5 polymorphisms in ESR2 (rs915057, rs1269056, rs1256033, rs3020450, and rs3020443) were selected. The risk of breast cancer for these polymorphisms was estimated among 542 cases and 1076 matched controls from the population-based Malmö Diet and Cancer cohort. The joint effect of these polymorphisms and enterolactone was estimated among those individuals about whom we had information on enterolactone blood concentration (365 cases and 728 controls). Breast cancer risk was not significantly associated with any of the selected polymorphisms. We found a tendency for an interaction between a polymorphism in intron 3 of ESR1 (rs2347867) and enterolactone concentration (P = 0.07). Breast cancer and enterolactone concentration were not associated among those homozygous for the major allele (A) (P = 0.93), whereas we found an inverse association among carriers of the minor allele (G) (P = 0.007). None of the other polymorphisms seem to modify the association between enterolactone and breast cancer. This study suggests that the protective association of enterolactone is reasonably robust across the investigated genotypes. The suggested interaction between enterolactone concentration and rs2347867 needs to be confirmed in larger samples.

Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women.

Results from epidemiological and experimental studies indicate that phytoestrogens may protect against breast cancer. Because one of the biological effects of phytoestrogens is probably estrogenic, it's possible that the preventive effect on breast cancer differs by estrogen receptor (ER) or progesterone receptor (PR) status of the tumor. We evaluated the associations between dietary phytoestrogen (isoflavonoids, lignans, and coumestrol) intake and risk of breast cancer and whether the ER/PR statuses of the tumor influence this relationship. In 1991-2 a prospective population-based cohort study among Swedish pre- and postmenopausal women was performed, making questionnaire data available for 45,448 women. A total of 1014 invasive breast cancers were diagnosed until December 2004. Cox proportional hazards models were performed to estimate multivariate risk ratios, 95% CI for associations with risk of breast cancer. Intakes of lignan, isoflavonoid, or coumestrol were not associated with breast cancer risk overall or before or after 50 y of age. The effects of lignans or isoflavonoids were independent of receptor status. However, intake of coumestrol was associated with decreased risk of receptor negative tumors (ER-PR-) but not positive tumors. The risk of ER-PR- tumors was significantly lower (50%) in women with intermediate coumestrol intake compared with those who did not consume any. In conclusion, we found no association between intake of isoflavonoids or lignans and breast cancer risk. Our results of a decreased risk of ER-PR- tumors in women with intermediate intake of coumestrol could be due to chance because of the low intake. The results should be confirmed in other studies.

Lignans and human health.

This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.

Monoclonal antibody-based time-resolved fluorescence immunoassays for daidzein, genistein, and equol in blood and urine: application to the Isoheart intervention study.

BACKGROUND: Time-resolved fluorescence immunoassays (TR-FIAs) for phytoestrogens in biological samples are an alternative to mass spectrometric methods. These immunoassays were used to test urine and plasma samples from individuals in a dietary intervention trial aimed at determining the efficacy of dietary isoflavones in reducing the risk of coronary heart disease in postmenopausal women. METHODS: We established murine monoclonal TR-FIA methods for daidzein, genistein, and equol. These assays could be performed manually or adapted to an automated analyzer for high throughput and increased accuracy. Analysis of urine was conducted on nonextracted samples. Blood analysis was performed on nonextracted samples for daidzein, whereas genistein and equol required diethyl-ether extraction. RESULTS: Comparison of monoclonal TR-FIA, commercial polyclonal antibody-based TR-FIA, and gas chromatography-mass spectrometry showed correlations (r, 0.911-0.994) across the concentration range observed in the Isoheart study (50 mg/day isoflavones). The concentrations of urinary daidzein and genistein observed during intervention demonstrated good compliance, and a corresponding increase in serum daidzein and genistein confirmed bioavailability of the isoflavone-rich foods; 33 of the 117 volunteers (28.2%) were classified as equol producers on the basis of their urinary equol concentration (>936 nmol/L), and significant differences in the numbers of equol producers were observed between Berlin and the 3 other European cohorts studied. CONCLUSIONS: The validated monoclonal TR-FIA methods are applicable for use in large-scale human phytoestrogen intervention studies and can be used to monitor compliance, demonstrate bioavailability, and assess equol producer status.

Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens.

Breast cancer is a major public health problem among women worldwide. Phytoestrogens and dietary fat composition are being investigated to elucidate the role of nutrition in breast cancer risk. Both epidemiological and rodent studies suggest that the chemopreventive effect of phytoestrogens depends on timing of exposure. We investigated spontaneous mammary tumor development in female heterozygous MMTV/c-neu (Tg.NK) mice upon isoflavone exposure on background diets rich in either n-6 or n-3 polyunsaturated fatty acids (PUFAs). Three different exposure protocols were used, either from conception to weaning, or from weaning onwards, or lifelong. Mice fed diets high in n-3 PUFAs developed mammary tumors 15 weeks later than mice fed n-6 PUFA diets. In the latter mice, isoflavone exposure from weaning onwards resulted in a significant decrease in tumor incidence and a delay in tumor onset. Therefore, the effects of phytoestrogen exposure on tumor formation appear to depend on the composition of the background diet and on the timing of exposure within the life cycle.

Phyto-oestrogen intake and plasma concentrations in South Asian and native British women resident in England.

Phyto-oestrogens, naturally occurring hormone-like chemicals in plant food, may play a protective role against hormone-related chronic diseases. South Asian migrants in the UK have a lower incidence of hormone-related cancer than their hosts but the extent to which this difference may be due to phytoestrogen intake is not known. The aim was to compare habitual phytoestrogen intake in first-generation South Asian migrant women and native British women. South Asian (n 221) and native British women (n 50) were recruited from general practitioner lists and were asked to provide monthly 24 h recalls for a period of 1 year. An enhanced phytoestrogen database was compiled using data from a literature search and unpublished data. A sub-sample of South Asian women (n 100) and the native British women (n 40) also provided blood samples every 3 months during the 1-year period. The median daily intakes (microg/d) of isoflavones (184.2 v. 333.9) and lignans (110.8 v. 148.8) were significantly lower in South Asians than in the native British (P<0.001, P=0.04 respectively). There were no significant differences in mean plasma isoflavone levels (nmol/l) but plasma enterolactone was significantly lower in the South Asians (13.9 (SD 17.5) v. 28.5 (SD 23.3), P<0.001). The main sources of phytoestrogens were bread and vegetables in both ethnic groups. Habitual phytoestrogen intake in South Asian and native British women was below 1 mg/d and was higher in the native British diet. The present study does not support the hypothesis that differences in phytoestrogen intake, or in circulating levels, could explain differences in hormone-related cancer risks between these two populations.

Prostatic phyto-oestrogen tissue levels in different Austrian regions.

INTRODUCTION: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. MATERIAL AND METHODS: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at -40 degrees C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. RESULTS: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5-76.4) or rural environment (median 15.7 range 0.6-140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6-47.4) and 9.3 (range 0.1-156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. CONCLUSION: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.

The effects of short-term oral phytoestrogen supplementation on the hypothalamic-pituitary-testicular axis in prostate cancer patients.

BACKGROUND: Here we evaluate the effects of oral phytoestrogen supplementation on hypothalamic-pituitary-testicular (HPT) axis in CaP patients. METHODS: We recruited 40 men about to undergo radical prostatectomy for CaP to receive either 240 mg of clover phytoestrogens or placebo daily for 2 weeks. Serum hormone levels were measured before and after treatment. In addition, recombinant cell bioassay was used to measure serum androgen bioactivity (ABA). RESULTS: Phytoestrogen treatment increased serum LH from mean of 3.4-5.2 IU, P = 0.03. Concomitantly, non-significant trend towards decline in serum T, cfT and ABA values was noted. However, mean serum LH/T ratio was upregulated from 0.20 to 0.48 IU/nM, P = 0.004, suggesting compensated hypogonadism. During the course of treatment, serum concentration of equol correlated strongly with the concomitant decrease in ABA (r = -0.586, P = 0.022). CONCLUSIONS: Phytoestrogen treatment interferes with HPT axis in CaP patients by inducing testicular resistance to LH and compensated hypogonadism.

Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden).

OBJECTIVE: Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. METHODS: In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. RESULTS: High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35-1.14) and 0.74 (95% CI: 0.41-1.32). CONCLUSIONS: Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation.

BACKGROUND: Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue. METHODS: Forty men with CaP, assigned for radical prostatectomy, received 240 mg of clover phytoestrogens or placebo daily for a 2-week period before their operation in a prospective and randomized study. Phytoestrogens were measured in plasma and prostate tissue by time-resolved fluoroimmunoassay (TR-FIA). RESULTS: All patients had low baseline phytoestrogen concentrations and only 35% had a detectable plasma concentration of equol. Oral supplementation with phytoestrogens induced a statistically significant (P<0.001) 23- and 7-fold increase in prostate tissue concentrations of the phytoestrogens genistein and daidzein, respectively. Supplemented patients demonstrated prostate tissue genistein and daidzein concentrations that were over twofold higher than their plasma. Interestingly, even though the placebo group did not receive phytoestrogen challenge, they also demonstrated twofold prostate tissue genistein and daidzein concentrations compared to their plasma values, suggesting that the prostate can concentrate available phytoestrogens. In addition, after the supplementation, 90% of the supplemented patients had a detectable plasma equol concentration. CONCLUSIONS: We conclude that prostate tissue can concentrate genistein and daidzein. Significant elevation of intraprostatic genistein and daidzein concentrations can be achieved with a short-term dietary phytoestrogen supplementation.

Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.