phytoestrogen

Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.: BMC Pharmacol. 2007 Sep 20; 7(1): 11 Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M

ABSTRACT: BACKGROUND: Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7. RESULTS: Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract. CONCLUSION: No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women.: J Med Assoc Thai. 2007 Jul; 90(7): 1274-80 Chandeying V, Lamlertkittikul S

OBJECTIVE: To evaluate the preliminary efficacy and safety of Pueraria mirifica (Kwao Keur Kao), phytoestrogen, for the alleviation of climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending with climacteric symptoms, such as hot flushes and night sweats, were invited to join the present study, conducted at the Menopausal Clinic, Hat Yai Regional Hospital. The patients were voluntarily enrolled and randomly received the raw material of Pueraria mirifica, oral 50 and 100 mg capsule, once daily for six months, as an open-label study. RESULTS: Of the 10 enrolled patients, 8 cases were completely evaluated. The modified Greene climacteric scale (MGCS) was satisfactorily decreased in both groups. The average scale declined from 44.1 at baseline, to be 26, 17, and 11.1 at 1-, 3-, and 6- month follow-up respectively. No other laboratory abnormalities, except one case had transiently increased the creatinine level, and one case of increased blood urea nitrogen. The mean serum estradiol was slightly increased, while the mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were nearly stable. CONCLUSION: Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal. women, but the data is insufficient to draw definite conclusions regarding the estrogenic effect.

[Effects of phytoestrogens on prostate cancer and benign prostatic hyperplasia]: Zhonghua Nan Ke Xue. 2007 May;13(5):457-61 Authors: Feng Y, Xia XY, Huang YF

Phytoestrogens are non-steroidal estrogens widely distributed in many kinds of plants. They are natural compounds structurally similar to estrogen and with estrogenic or anti-androgenic activities. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent and associated with age. Recently, in many epidemiological and experimental researches, it has been reported that phytoestrogens play a role in the prevention and treatment of PCa and BPH. Regulation of sexual hormones, inhibition of cell proliferation, induction of cell apoptosis and anti-oxidation of such plant estrogens may be involved in the mechanisms.

PMID: 17569267 [PubMed - in process]

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?:

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?

Mol Nutr Food Res. 2007 Jun 20;

Authors: Power KA, Thompson LU

Consumption of phytoestrogen (PE)-rich foods (i. e., soy and flaxseed (FS)) is increasing because of their suggested health benefits. However, recent studies raise concern over the safety of soy and its isoflavones, particularly genistein (GEN), for postmenopausal breast cancer (BC), due to their potential stimulatory effects on human breast tissue and on the growth of existing tumors in rodents. FS, rich in PE lignans, which is metabolized to the mammalian lignans enterolactone (ENL) and enterodiol (END), has consistently been shown to have tumor inhibitory effects in a human clinical trial as well as rodent BC models. Using the preclinical athymic mouse postmenopausal BC model, combining FS with soy protein or GEN with END and ENL, was found to negate the tumor stimulatory effects of soy protein or GEN alone. The mechanism may be related to the modulation of estrogen receptor and MAPK signaling pathways. If these studies can be confirmed in clinical trials, then consumption of combined soy and FS, or their PEs, may reduce the tumor growth stimulatory effect of soy or GEN. This may indicate that if soy is consumed with lignan-rich foods, it may continue to induce its other beneficial health effects, without inducing adverse effect on postmenopausal BC.

PMID: 17579892 [PubMed - as supplied by publisher]

Phytoestrogens: perpetrators or protectors?: Future Oncol. 2007 Jun;3(3):307-318 Authors: Martin JH, Crotty S, Nelson PN

Phytoestrogens are estrogen-like substances produced by plants that account for some of the constituents present in vegetation that may be responsible for the health benefits of a diet rich in fruit and vegetables. Phytoestrogens have a plethora of different actions that they are capable of exerting on cellular metabolism. This review will focus on some of the major nonestrogen receptor-mediated cellular effects used by phytoestrogens and will draw attention to the fact that while they may have a number of beneficial effects, particularly in offering a protective effect against some hormone-dependent cancers, such as breast and prostate cancer, they may also have possible unfavorable effects by interfering with the functioning of normal cellular activities such as receptor-mediated signal transduction and DNA replication, as well as being genotoxic, mutagenic and promoting the proliferation of some cancer cells.

Mitochondrial oxidant signalling in Alzheimer's disease.: J Alzheimers Dis. 2007 May;11(2):175-81 Authors: Viña J, Lloret A, Vallés SL, Borrás C, Badía MC, Pallardó FV, Sastre J, Alonso MD

The role of free radicals in Alzheimer disease pathophysiology has been appreciated for a long time. Originally, radicals were considered as causative of oxidative damage. More recently their role as signalling molecules in this, as well as in other fields of free radical biology, has been underscored. Mitochondria are both generators and targets of radical damage in aging. In this paper we review evidence that radicals generated in mitochondria in the presence of Abeta are signals that trigger both the mitochondrial and the extra-mitochondrial pathways of apoptosis. There are gender specific differences in mitochondrial Abeta toxicity: mitochondria from young (but not from old) females appear to be protected. 17-beta Estradiol or phytoestrogens like genistein prevent the formation of oxidants by mitochondria and protect against mitochondrial Abeta toxicity. Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease.

Dietary phytoestrogen intake and cognitive function in older women.: J Gerontol A Biol Sci Med Sci. 2007 May;62(5):556-62 Authors: Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, van der Schouw YT

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Phytoestrogens and Coronary Microvascular Function in Women with Suspected Myocardial Ischemia: A Report from the Women's Ischemia Syndrome Evaluation (WISE) Study.: J Womens Health (Larchmt). 2007 May;16(4):481-8 Authors: Pepine CJ, Von Mering GO, Kerensky RA, Johnson BD, McGorray SP, Kelsey SF, Pohost G, Rogers WJ, Reis SE, Sopko G, Bairey Merz CN

Aims: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. Methods: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. Results: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. Conclusions: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Phytoestrogens in clinical practice: a review of the literature.: Fertil Steril. 2007 May 8; Authors: Tempfer CB, Bentz EK, Leodolter S, Tscherne G, Reuss F, Cross HS, Huber JC

OBJECTIVE: To review clinical studies assessing the effect of phytoestrogen supplementation on the signs and symptoms of the climacteric syndrome and on the incidence of breast cancer, cardiovascular disease, and skeletal fractures. DESIGN: Literature research using PubMed and the Cochrane controlled trials register. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Six systematic reviews and meta-analyses of 25 randomized, controlled trials (RCTs) assessing the use of phytoestrogens for the treatment of the climacteric syndrome were identified. Systematic reviews of RCTs show contradictory results, and meta-analyses demonstrate no statistically significant reduction of vasomotor symptoms for phytoestrogens. Individual RCTs report significant reductions in vasomotor symptoms for red clover and soy phytoestrogens. In selected patient populations, such as in women with early natural postmenopause and mild to moderate vasomotor symptoms, a systematic review of five RCTs found a significant reduction of hot flashes in five out of five RCTs. Twenty-two case-control and cohort studies examined the incidence of breast cancer among women with and without a diet high in phytoestrogens. A meta-analysis of 21 studies found a significantly reduced incidence of breast cancer among past phytoestrogen users. RCTs document beneficial effects of phytoestrogens on surrogate parameters such as bone mineral density, vasodilation, platelet aggregation, insulin resistance, and serum concentrations of triglycerides, high-density lipoprotein, and low-density lipoprotein. None of the available RCTs documents a protective effect of phytoestrogens for the clinical end points of breast cancer, bone fracture, or cardiovascular events. CONCLUSION(S): Based on the available evidence, phytoestrogens should only be used in selected women, i.e., those presenting with mild to moderate vasomotor symptoms in early natural postmenopause. None of the compounds investigated so far have been proven to protect against breast cancer, bone fracture, or cardiovascular disease.

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.: Environ Health Perspect. 2007 Jan;115(1):116-21 Authors: Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britton JA, Chelimo C, Godbold J, Biro F, Kushi LH, Pfeiffer CM, Calafat AM

BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development.