Comprehensive estrogenic/anti-estrogenic, anticancer, mutagenic/anti-mutagenic, and genotoxic/anti-genotoxic activity studies on chemically characterized black poplar and Eurasian aspen propolis types.

Propolis is mainly composed of plant resins, and its type is named according to the primary plant origin in its composition. Identification of propolis botanical origin is essential for predicting and repeating its pharmacological activity because of the variations in chemical composition. This study aimed to compare chemical composition of black poplar (Populus nigra L.) type-propolis (PR1 and PR2) and Eurasian aspen (P. tremula L.)-type propolis (PR3) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique and to evaluate their biological activity profiles. According to LC-MS/MS results, in addition to marked caffeic acid phenethyl ester content in PR1 and PR2, flavonoid aglycones such as pinocembrin, chrysin, pinobanksin, and galangin were found to be dominant in these samples. On the other hand, PR3 contained relatively high concentrations of phenolic acids such as ferulic acid, p-coumaric acid, and trans-cinnamic acid. The anti-estrogenic activity test showed that PR2 exerted the highest anti-estrogenic activity by inhibiting cell proliferation by 44.6%. All propolis extracts showed anticancer activity, which was justified by decreasing activity on the 3D spheroid size in a concentration-dependent manner. Besides, all extracts showed moderate or potent antimutagenic activity in Salmonella typhimurium TA98 and TA100 strains with and without metabolic activation, respectively. In addition, the Comet assay results revealed that propolis extracts have a geno-protective effect against H2O2-induced DNA damage in CHO-K1 cells at 0.625 and 1.25 µg/mL concentrations. Overall, the result of this study may help in preparing standardized propolis extracts and developing products with defined pharmacological benefits in the food supplements industry.

Apigenin acts as a partial agonist action at estrogen receptors in vivo.

The flavone apigenin is widely distributed in vegetables and fruits and has a variety of pharmacological effects. However, there is no definitive scientific evidence that apigenin could act as a phytoestrogen and exert exerting estrogenic or antiestrogenic efficacy in vivo. Therefore, this study was established an ovariectomy (OVX) and estrogenized mouse model to evaluate the effects of apigenin on reproductive target tissues. Our data demonstrated that apigenin could exert a double-directional adjusting estrogenic effect in vivo. Specifically, treatment with apigenin reversed the weight changes caused by abnormal estrogen levels and altered the status of vaginal epithelial cells via the estrogen receptors. In addition, we found that apigenin exhibited a significant estrogenic activity, as indicated by the reversal of uterine atrophy. Apigenin treatment could also regulate the target tissue coefficient changes and estrogen disorders caused by excessive estrogen. Importantly, the administration of apigenin could upregulated the estrogen receptor (ER) α and ER ß expression as a partial agonist. Our results demonstrate that apigenin has a double directional adjusting function in different physiological environments.

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.).

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL-1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.

Identification of 10-dehydrooxyglycyuralin E as a selective human estrogen receptor alpha partial agonist.

Selective estrogen receptor modulators (SERMs) act as either agonist or antagonist of estrogen receptor (ER) in a tissue selective manner and have been used in several diseases such as breast cancer, postmenopausal syndrome, osteoporosis, and cardiovascular diseases. However, current SERMs may also increase the risk of serious side effects and trigger drug resistance. Herein, a screening program, that was designed to search for novel SERMs, resulted in the identification of a series of 2-arylbenzofuran-containing compounds that are ligands for ERα, when applying the Gaussia-luciferase reporter assay. One of these compounds, 10-dehydrooxyglycyuralin E (T9) was chemically synthesized. T9 showed anti-estrogenic/proliferative activity in ERα-positive breast cancer cells. Pretreatment of T9 prevented the mRNA expression of GREB1, which is an estrogen response gene. Furthermore, by an in silico docking simulation study we demonstrated that T9 showed interactions directly to ERα. Taken together, these results demonstrated that T9 is a candidate of SERMs and a useful seed compound for the foundation of the selective activity of SERMs.

Computational insights on agonist and antagonist mechanisms of estrogen receptor α induced by bisphenol A analogues.

Structural analogues of bisphenol A (BPA) have become widely used as alternatives in BPA-free products. Most toxicological investigations have focused on the estrogenic activities of these analogues, which have been considered as potential environmental estrogens. However, recent studies revealed that certain BPA analogues could dramatically inhibit the proliferation of breast cancer cells, and exhibited strong anti-estrogenic effects compared with the antagonist 4-hydroxytamoxifen (OHT). Thus, we adopted computational models combining molecular dynamics simulations and binding free energy calculations to explore the underlying molecular basis of BPA analogues binding to estrogen receptor α (ERα). We also evaluated ligand-induced structural rearrangements of ERα at the atomic level. Conformational analyses showed that induced-fit H-bonding recognition by Thr347 was an important factor distinguishing antagonist from agonist BPA analogues. Moreover, antagonists of BPA analogues could indirectly induce the structural reposition of key helix 12 and produce an antagonistic conformation of ERα. Compared with OHT, the binding affinity of BPA analogues is stronger for antagonists than agonists. Taken together, we therefore propose computational indicators for screening of anti-estrogenic activities of BPA analogues, which may be beneficial for predicting the estrogenic or anti-estrogenic effects of BPA alternatives.

Efficient synthesis of a multi-substituted diphenylmethane skeleton as a steroid mimetic.

Steroids are important components of cell membranes and are involved in several physiological functions. A diphenylmethane (DPM) skeleton has recently been suggested to act as a mimetic of the steroid skeleton. However, difficulties are associated with efficiently introducing different substituents between two phenyl rings of the DPM skeleton, and, thus, further structural development based on the DPM skeleton has been limited. We herein developed an efficient synthetic method for introducing different substituents into two phenyl rings of the DPM skeleton. We also synthesized DPM-based estrogen receptor (ER) modulators using our synthetic method and evaluated their ER transcriptional activities.

Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents.

Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-ß (ER-ß) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49µM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-ß; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.

A Fucus vesiculosus extract inhibits estrogen receptor activation and induces cell death in female cancer cell lines.

BACKGROUND: We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biologically relevant anti-tumorigenic effects in estrogen receptor (ER)-dependent and -independent female cancer cell lines. METHODS: The CALUX® assay was used to determine the effect of a F. vesiculosus extract (FVE) on activation of the ER. Aromatase enzymatic activity was measured to determine the potential effect of FVE on estradiol (E2) biosynthesis. Transcriptional activity profiling of 248 genes involved in cancer, immunity, hormonal regulation, protein phosphorylation, transcription, metabolism, and cellular structure was conducted using the NanoString nCounter® analysis system in FVE-treated breast, ovarian and endometrial cancer cell lines. The effects of FVE on cell viability, morphology, membrane integrity, mitochondrial toxicity, induction of apoptotic and autophagic markers, and cell signaling were also analyzed. RESULTS: In co-treatments with 12.5 pM (EC50) E2, FVE (2 %) reduced ER activation by 50 %, exhibiting potent ER antagonistic effects. FVE inhibited aromatase activity in an in vitro assay (IC50 2.0 %). ER-dependent and -independent cancer cell lines showed significantly decreased viability that correlated with increasing FVE concentrations and altered morphological features suggestive of apoptosis and autophagy. Expression of genes that were significantly altered by FVE (p < 0.05) revealed predominantly apoptotic, autophagic and kinase signaling pathways. FVE also effectively inhibited the phosphorylation of Akt, resulting in reduced mTORC1 activities to stimulate autophagy in cells. Concentration-dependent cleavage of PARP and induction of caspase-3 and -7 activities were observed in MDA-MB-231 cells supporting a role for FVE in the promotion of apoptosis. CONCLUSIONS: Our study provides new insights into the anti-estrogenic activity of F. vesiculosus. Moreover, the induction of autophagy and apoptosis on breast, endometrial and ovarian cancer cell lines suggests additional anti-tumorigenic actions of FVE that are independent of ER status in female cancers.

Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 µg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17ß-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 µg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment.

The estrogenic and androgenic potential of pyrethroids in vitro. Review.

Synthetic pyrethroids are used worldwide as insecticides. Their metabolites are regularly detected in the urine of adults and children from the general population. There is increasing concern that they may induce sex-hormone disrupting effects. The present work reviews available published information on the (anti)estrogenic and (anti)androgenic activity of pyrethroids in in vitro screening tests. In recent years, a large number of pyrethroids have been evaluated using various common testing methods. In tests using recombinant yeast or mammalian cells, the pyrethroids were found to be essentially negative or weakly estrogenic. More inconsistent results were found regarding their estrogenic action in proliferation tests. Conflicting findings were also reported across studies and/or assays which evaluated their anti-estrogenic or anti-androgenic potential. Some studies have suggested that certain pyrethroids may have potential antagonist activity. However, no strong interaction with the estrogenic or androgenic pathway was reported. The present review confirms the interest in performing a screening battery and in adopting an integrative approach for identifying the potential of different compounds from a chemical family to interfere with the endocrine system.

Changes in the components and biotoxicity of dissolved organic matter in a municipal wastewater reclamation reverse osmosis system.

The characteristics of dissolved organic matter (DOM) and the biotoxicity of these components were investigated in a municipal wastewater reclamation reverse osmosis (mWRRO) system with a microfiltration (MF) pretreatment unit. The MF pretreatment step had little effect on the levels of dissolved organic carbon (DOC) in the secondary effluent, but the addition of chlorine before MF promoted the formation of organics with anti-estrogenic activity. The distribution of excitation emission matrix (EEM) fluorescence constituents exhibited obvious discrepancies between the secondary effluent and the reverse osmosis (RO) concentrate. Using size exclusion chromatography, DOM with low molecular weights of approximately 1.2 and 0.98 kDa was newly formed during the mWRRO. The normalized genotoxicity and anti-estrogenic activity of the RO concentrate were 32.1 ± 10.2 µg4-NQO/mgDOC and 0.36 ± 0.08 mgTAM/mgDOC, respectively, and these values were clearly higher than those of the secondary effluent and MF permeate. The florescence volume of Regions I and II in the EEM spectrum could be suggested as a surrogate for assessing the genotoxicity and anti-estrogenic activity of the RO concentrate.

Phenolic constituents of the Bangladeshi medicinal plant Pothos scandens and their anti-estrogenic, hyaluronidase inhibition, and histamine release inhibitory activities.

Extracts from the stem and roots of the Bangladeshi medicinal plant Pothos scandens L. (Araceae) were isolated, and three hemiterpene glucoside aromatic esters, pothobanosides A (1), B (2), and C (3), and a phenylisobutanoid, pothobanol (4), along with 14 known compounds, were characterized. The isolates were tested for their estrogenic/anti-estrogenic activity using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D, and syringoyl derivatives (2, 3, and canthoside B) showed strong inhibitory activity against both cell lines. Their less oxygenated analogs (1, and markhamioside F) were almost inactive. The isolates were also evaluated for hyaluronidase and histamine release inhibitory activities, and pothobanoside A (1) showed significant hyaluronidase inhibitory activity among the isolated compounds, which was similar to that of the positive control rosmarinic acid. Because hyaluronidase produces an angiogenic response that has been implicated in tumor invasiveness and metastasis, 1 could be valuable as an anti-tumor compound with a different mechanism of action from related compounds (2, 3). Pothobanoside C (3) and pothobanol (4) were also found to inhibit histamine release to a similar degree to the positive control epigallocatechin 3-O-(3"-O-methyl)-gallate. The histamine release inhibitory potency of these isolates may support the traditional uses of this plant in folk medicine.

Characterization and biotoxicity assessment of dissolved organic matter in RO concentrate from a municipal wastewater reclamation reverse osmosis system.

Reverse osmosis (RO) concentrate from municipal wastewater reclamation reverse osmosis (mWRRO) system containing organic compounds may associate with toxic risk, and its discharge might pose an environmental risk. To identify a basis for the selection of feasible technology in treating RO concentrates, the characteristics and biotoxicity of different fractions of dissolved organic matter (DOM) in RO concentrates from an mWRRO system were investigated. The results indicated that the hydrophilic neutrals (HIN), hydrophobic acids (HOA) and hydrophobic bases (HOB) accounted for 96% of the dissolved organic carbon (DOC) of the total DOM in the RO concentrate. According to the SEC chromatograph detected at 254 nm wavelength of UV, the DOM with molecular weight (MW) 1-3 kDa accounted for the majority of the basic and neutral fractions. The fluorescence spectra of the excitation emission matrix (EEM) indicated that most aromatic proteins, humic/fulvic acid-like and soluble microbial by-product-like substances existed in the fractions HOA and hydrophobic neutrals (HON). The genotoxicity and anti-estrogenic activity of the RO concentrate were 1795.6 ± 57.2 µg 4-NQOL(-1) and 2.19 ± 0.05 mg TAM L(-1), respectively. The HIN, HOA, and HOB contributed to the genotoxicity of the RO concentrate, and the HIN was with the highest genotoxic level of 1007.9 ± 94.8 µg 4-NQOL(-1). The HOA, HON, and HIN lead to the total anti-estrogenic activity of the RO concentrate, and HOA occupied approximately 60% of the total, which was 1.3 ± 0.17 mg TAM L(-1).

Estrogenic and anti-estrogenic activities of hispolon from Phellinus lonicerinus (Bond.) Bond. et sing.

Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17ß-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (-) MDA-MB-231 cells at the concentration of 5.00×10(-5) M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERß at a concentration of 1.00×10(-6) M. The ERß-binding ability of hispolon was larger than ERα in the concentration range of 1.00×10(-9) M and 1.00×10(-7) M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10×10(-6) mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERß docked complexes were -7.93 kcal/mol and -7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.

Anti-estrogenic activity formation potential assessment and precursor analysis in reclaimed water during chlorination.

Chlorination was reported to increase the anti-estrogenic activity in reclaimed water from domestic wastewater treatment plants, which may add to the risk of reclaimed water reuse. In order to assess the anti-estrogenic disinfection by-product (DBP) precursors, the anti-estrogenic activity formation potential (AEAFP) during chlorination was studied. Firstly, the conditions for the experimental measurement of AEAFP were determined. A 24-h chlorination experiment was applied for AEAFP measurement. After chlorination, dechlorination using reductive reagents led to significant loss of anti-estrogenic activity formation. In addition, as the presence of ammonia nitrogen and other major chlorine consumers would result in lower anti-estrogenic activity formation, a basic chlorine dose of 3× DOC (mg-Cl2 L(-1)) was adequate for completely transforming the anti-estrogenic DBP precursors while an extra chlorine dose of 8× ammonia-nitrogen + 5× nitrite-nitrogen (mg-Cl2 L(-1)) should be added when there was a high level of ammonia nitrogen and nitrite nitrogen in the reclaimed water. Therefore, 24-h chlorination without dechlorination or using only non-reductive quenching reagents (e.g. ammonium) for dechlorination and a total chlorine dose of 3× DOC + 8× ammonia nitrogen + 5× nitrite nitrogen (mg-Cl2 L(-1)) should be fulfilled for the AEAFP measurement. Moreover, the AEAFP (0.2-2.1 mg-TAM L(-1)) of the reclaimed water samples (n = 20) were further analyzed. The AEAFP was highly correlated to UV254 and the fluorescence volume in excitation emission matrix fluorescence spectrum which can be used as surrogates to indicate the level of the AEAFP and assess the precursors in reclaimed water.

Transformation of anti-estrogenic-activity related dissolved organic matter in secondary effluents during ozonation.

Anti-estrogenic activity of dissolved organic matter (DOM) in reclaimed water is gaining increasing attention. In this study, anti-estrogenic activity removal efficiency by ozonation in the tertiary treatment process of domestic wastewater was investigated. The anti-estrogenic activity in the secondary effluents used in this study ranged between 0.95 and 2.00 mg-TAM L(-1) and decreased significantly after ozonation. The removal efficiency of anti-estrogenic activity at a dose of 10 mg-O3 L(-1) was 65-87%. The removal of the anti-estrogenic activity was highly correlated with the removal of UV254, suggesting that UV254 can be used as a surrogate for anti-estrogenic activity during ozonation. The results of size exclusion chromatography of the wastewater samples during ozonation showed that the UV254 absorbance of the DOM fraction with large apparent molecular weight (MW) around 7.6 k Da dropped significantly, and the DOM fraction was suspected to be humic substances which have been previously identified as anti-estrogenic constituents in secondary effluents. The excitation emission matrix fluorescence spectra of the wastewater samples proved that humic substances existed in the DOM and indeed reacted with the ozone. With the help of two-dimensional correlation of Fourier transform infrared, it was confirmed that the aromatic structures in the DOM were largely destroyed by ozonation. Therefore, it was suggested that the destruction of the aromatic structures in the DOM was related to the removal of the anti-estrogenic activity.

Removal potential of anti-estrogenic activity in secondary effluents by coagulation.

Anti-estrogenic activity in wastewater is gaining increased attention because of its endocrine-disrupting function. In this study, the level and removal efficiency by coagulation of anti-estrogenic activity in secondary effluents of domestic wastewater treatment plants were studied. Anti-estrogenic activity was detected in secondary effluent samples at a tamoxifen (TAM) equivalent concentration level of 0.38-0.94 mg-TAML(-1). Dissolved organic matters (DOM) with the molecular weight (MW) less than 3000 Da in hydrophobic acids (HOA) and hydrophobic neutrals (HON) fractions of the secondary effluent were the key fractions related to anti-estrogenic activity. Coagulation with FeCl(3) and polyaluminium chloride (PAC) can remove the anti-estrogenic activity of the secondary effluents, but the removal efficiency was limited. The removal efficiency using FeCl(3) coagulant was higher than that induced by PAC. Dissolved organic carbon was continuously removed with increased coagulant dose (0-120 mg L(-1) FeCl(3) or 0-60 mg L(-1) PAC). However, the removal of anti-estrogenic activity was not enhanced further when the coagulant concentration was beyond a critical value (30 mg L(-1) FeCl(3) or 10 mg L(-1) PAC). The highest removal of anti-estrogenic activity was about 36% by FeCl(3) and 20% by PAC. Size exclusion chromatography results indicated difficulty in removing DOM with MW less than 3000 Da in the secondary effluent during coagulation even at a high coagulant concentration, which led to low removal efficiency of anti-estrogenic activity.

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

Semente de linhaça e o efeito de seus compostos sobre as células mamárias / Flaxseed and the effect of his compound on human breast cell

O câncer de mama é uma doença que afeta principalmente as mulheres e segundo as estatísticas esta vem aumentando com certa frequência nos países ocidentais, e isto tem preocupado a comunidade científica. Esta doença está associada a diversos fatores de risco, sendo a dieta um fator que tem demonstrado relação com a promoção de câncer de mama. Uma alimentação rica em substância funcional tem sido alvo de atenção, pois os fitoestrógenos têm mostrado através de estudos experimentais, propriedades benéficas à saúde, e parece contribuir para a redução do risco de câncer de mama. Alimentos como a semente de linhaça tem sido objeto de estudo, já que contêm substâncias consideradas como quimioprotetora e sua estrutura química assemelha-se ao estrogênio humano e compete com este pelo seu sítio de ligação. De acordo com os estudos experimentais, realizados com animais e humanos, a semente de linhaça é rica em lignana e outros componentes, que apresentaram ter efeito fracamente estrogênico e antiestrogênico, mostrando exercer influência na diminuição do risco de câncer de mama.

The breast cancer is a disease that affects especially women, and according to statistics, this is increasing with certain frequency in western country and it has been concerning the scientific society. This disease is associated with various factors of risk, and diets have being considered a factor that has promoted breast cancer. Food rich in functional substances has drawn attention, because phytoestrogens have showed, through experimental studies, beneficial properties for health and appeared to contribute for the decrease of breast cancer risk. Food with flaxseed has been object of study, because it contains substances called chemoprotective and its chemistry structure resembles human estrogens and competes with its link site. According to the experimental studies made in animals and humans, flaxseed is rich in lignans and other components, that seem to have weak estrogenic/antiestrogenic effect showing to exert influence in the decreasing of breast cancer risk.