• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9085-9091
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• 2014

Background: Epidemiology studies have shown an inconclusive relationship between phytoestrogen intake and ovarian cancer risk and there have been no relevant meta-analyses directly regarding this topic. The purpose of the present meta-analysis was therefore to investigate any association between phytoestrogen intake and ovarian cancer in detail. Materials and Methods: We conducted a search of PubMed, EMBASE, EBSCO, the Cochrane Library, CNKI and Chinese Biomedical Database (up to April 2014) using common keywords for studies that focused on phytoestrogen and ovarian cancer risk. Study-specific risk estimates (RRs) were pooled using fixed effect or random-effect models. Results: Ten epidemiologic studies were finally included in the meta-analysis. The total results indicated higher phytoestrogen intake was associated with a reduced ovarian cancer risk (RR, 0.70; 95%CI: 0.56-0.87). The association was similar in sensitivity analysis. Meta regression analysis demonstrated sources and possibly types and regions as heterogeneous factors. Subgroup analysis of types, sources and regions showed that isoflavones (RR: 0.63; 95%CI: 0.46, 0.86), soy foods (RR: 0.51; 95%CI: 0.39, 0.68) and an Asian diet (RR: 0.48; 95%CI: 0.37, 0.63) intake could reduce the incidence of ovarian cancer. Conclusions: Our findings show possible protection by phytoestrogens against ovarian cancer. We emphasize specific phytoestrogens from soy foods, but not all could reduce the risk. The habit of plentiful phytoestrogen intake by Asians is worthy to recommendation. However, we still need additional larger well designed observational studies to fully characterize underlying associations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5937-5946
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• 2012

The term endocrine disruptors is used to describe a variety of natural and manmade substances that have the capacity to potentially interfere with and modify the normal physiology of endocrine system either by mimicking, blocking or modulating the actions of natural endogenous hormones. The rising incidence of breast cancer over the last 50 years and the documented higher incidence in urban as compared to rural areas suggest a relationship to the introduction and increased use of xenoestrogens in our environment. The literature has developed over the last decades where initial experiments on endocrine disruptors did not support an involvement in breast cancer, and then evidence mounted implicating various environmental factors including hormones, endocrine disrupting chemicals and non-endocrine disrupting environmental carcinogens in the pathogenesis of breast cancer. Available data support the hypothesis that exposure to endocrine disruptors in utero leaves a signature on mammary gland morphogenesis so that the resulting dysgenic gland becomes more predisposed to develop tumors upon exposures to additional insults later on during life. Exceptionally, exposure to phytoestrogens could be beneficial to human health. Most of the available data are from well developed countries while the developing countries are still understudied regarding these issues. Here, we raise a note of caution about potential role of environmental toxins including endocrine disruptors in breast cancer development and call for serious measures to be taken by all involved parties in the developing world.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6093-6095
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• 2012

Background: Phytoestrogens may be an alternative therapy in control of menopausal symptoms but their definite effects on breast tissue must be determined. Our study aimed to define the clinical and ultrasonographic changes of the breast after use of soy isoflavones in menopausal women. Materials and Methods: Menopausal women with hot flashes were randomly grouped as cases and controls and cases received soy isoflavones for 12 weeks. Breast examination (BE) and ultrasonography (US) were done at 0, 6 and 12 weeks. Tenderness and nodularity on BE were graded 1-4 by breast surgeons. Results: There were 30 women in the case and 26 in the control group. The mean age was 51.3 years and the mean age of menopause was 49.2 years. There was no change in the BE and US at 6 weeks in controls. In the case group, 10% had grade 1 tenderness and 13.3% grade 2 tenderness and grade 1 nodularity in BE accompanied with diffuse small cysts in US. At 12 weeks, there was no change in BE and US in the 2 groups. Conclusions: There was no statistically significant difference in the BE of the 2 groups at 6 and 12 weeks (p value=0.36 and 0.41 for nodularity and tenderness respectively) and in the US results. Although the literature contains many facts concerning PEs and the breast, further prospective studies are needed to identify structural breast changes produced by PEs in order to identify the appropriate dosage and indications of use.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.503-511
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• 2018

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS ($0.1-10{\mu}M$), BPA ($0.1-10{\mu}M$) and E2 ($0.01-0.0001{\mu}M$) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem ($30{\mu}M$) or DIM ($15{\mu}M$). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as $eIF2{\alpha}$ and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.

• Journal of Dairy Science and Biotechnology
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• v.36 no.2
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• pp.81-94
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• 2018

This review discusses the characteristics of major lignans and related studies and provides a basis for future studies. Lignans are present in various food products consumed daily, such as flaxseed and other seeds, vegetables, fruits, and beverages including coffee, tea, and wine. Lignans are natural phytoestrogens with a structure similar to that of secoisolariciresinol (Seco), mataireinol (Mat), pinoresinol (Pin), medioresinol (Med), lariciresinol (Lari), and syringaresinol, which is then converted to enterodiol (END) and enterolactone (ENL), which are mammalian lignans and the primary biologically active enterolignans, by the intestinal microflora. The associations between lignans and a decreased risk of cardiovascular disease are promising; however, they are not yet well-established, probably owing to low lignan intake in habitual Western diets. Nonetheless, these associations were more prominent at the higher doses in interventional studies. Many studies on humans and animals have reported the benefits of lignan consumption in protecting against CVD and metabolic syndrome by reducing lipid and glucose concentrations. END and ENL reportedly exert protective effects including phytoestrogenic, antioxidant, anti-inflammatory, and anticancer effects through various mechanisms. Moreover, lignans reportedly exert beneficial effects in breast, colon, and prostate cancer and osteoporosis have reported that. However, future studies are required to confirm the association between lignan and disease.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.512-520
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• 2005

Phytoestrogens, especially Yak-kong or soybean-derived isoflavones have been traditionally used as a supplement of estrogen for preventing postmenopausal osteoporosis in oriental folk medicine. In a previous study, we demonstrated that as Yak-kong and soybean increased MG-63 human osteoblastic cell proliferation, the expression of estrogen receptor $\alpha\;and\;beta\;(ER\;\alpha:\;ER\;\beta$) both were increased. However, the increased level of ER $\alpha$ is much higher than that of ER$\beta$. To determine whether the altered level of ER $\alpha$ expression affects Yak-kong or soybean induced MG-63 cell proliferation, we established cell lines stably expressing either ER $\alpha$ or antisense ER $\alpha$ RNAs. Increased expression of ER a in MG- 63 cells (ER $\alpha$-MG63) enhanced Yak-kong or soybean induced proliferation which paralleled with the enhanced expression of IGF-I. Inhibition of ER $\alpha$ expression by antisense $ER\;\alpha\;RNAs\;(As-ER\;\alpha-MG63$) caused these cells to insensitize Yak- kong or soybean induced proliferation and IGF-I expression. Furthermore, the comparable effects between Yak-kong and the combined treatment of genistein and daidzein at $0.5\;{\times}\;10^{-8}M$, which is a concentration of these two isoflavones similar to Yak-kong at 0.001 mg/ml, on cell proliferation and IGF-I expression in $ER\;\alpha-MG63\;or\;As-ER\;\alpha-MG63$ cells demonstrate that ER $\alpha$ plays an important, active role in MG-63 cell proliferation induced by phytoestrogens, especially Yak-kong or soybean derived isoflavones.

• Journal of Plant Biotechnology
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• v.5 no.3
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• pp.149-155
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• 2003

Metabolic engineering for production of isoflavones in nonlegume plants could distribute the health benefits of these phytoestrogens in more widely-consumed grains. Series of investigation to check the ability of the heterologous isoflavone synthase enzyme to interact with the endogenous phenylpropanoid pathway have been conducted. Overall, results provide possibility of production of isoflavonoids in several plant tissue systems including soybean and nonlegumes. In tissue that undergoes naturally enhanced synthesis of anthocyanins, genistein production was enhanced. In a monocot cell system, introduced expression of a transcription factor regulating genes of the anthocyanin pathway was effective in conferring the ability to produce genistein in the presence of the isoflavone synthase gene. However, in this case the intermediate accumulated to high levels indicating an inefficiency in its conversion. Introduction of a third gene, chalcone reductase, provided the ability to synthesize an additional substrate of isoflavone synthase resulting in production of the isoflavone daidzein. These research efforts provide insight into requirements for metabolic engineering for isoflavone production in nonlegume dicot and monocot tissues.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.741-745
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• 2006

In our efforts to discover novel phytoestrogens to treat menopausal symptoms, eleven furanocoumarins were isolated from Angelica dahurica and tested for their estrogenic activity on the Ishikawa cell line. Among the compounds tested, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin showed strong abilities to induce alkaline phosphatase (AP) with $EC_{50}$ values of 1.1 and $0.8\;{\mu}g/mL$, respectively, whereas the other nine furanocoumarins were weakly or only slightly active.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7001-7010
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• 2014

Isoflavones are phytoestrogens and natural plant compounds which are similar to 17-${\beta}$-estradiol in chemical structure. It is known that they can act as estrogen agonists or antagonists, depending on endocrine estrogenic levels, but actions of isoflavones are rather complex due to large number of variables such as chemical structures and mechanisms. Some hypotheses on biological mechanisms have not satisfactorily been confirmed to date and human epidemiological and experimental studies have been relatively limited. Nevertheless, isoflavones and isoflavone rich foods have become a focus onf interest due to positive health benefits on many diseases, especially prevention of hormone-related cancers, cardiovascular disease, osteoporosis, and adverse postmenopausal symptoms, and improvement of physiological condition such as maintaining cognitive function. This review provides an overview of chemistry, analytical techniques (focused on human biospecimens), functions including biological mechanisms, and effects of isoflavones, on the basis of the available meta-analysis and review articles and some original articles, on health and cancer.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2004.05a
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• pp.256-256
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• 2004