phytoestrogens and Neoplasms

Geroprotection is defined as protection from the adverse effects of aging. The need for geroprotection implies changes towards individually tailored interventions that preserve an individual's independence, physical function, and cognition. Genistein, a phytoestrogen obtained from soya, has been reported to have beneficial properties on age-related diseases such as neurodegenerative and cardiovascular diseases or cancer. Indeed, genistein is a multimodal agent: it acts as a cancer protective agent, promoting apoptosis and cell cycle arrest, and inhibiting angiogenesis and metastasis, but it also acts as an antioxidant, anti-inflammatory, and anti-amyloid-β and autophagy promoter. Altogether, these properties make genistein a possible treatment for the specific aspects of age-related diseases such as hypertension, metabolic diseases, Alzheimer's disease, and osteoporosis.

Topics: Amyloid beta-Peptides; Genistein; Geroscience; Humans; Neoplasms; Phytoestrogens

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

Topics: Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Humans; Lignans; Neoplasms; NF-kappa B; Phytoestrogens

Recent studies have outlined the potential role of dietary factors in patients who have survived cancer.. The aim of this study was to summarize the evidence of the relation between dietary intake of phytoestrogens and their blood biomarkers and, overall, cancer-specific mortality and recurrence in patients with cancer.. A systematic search of PubMed, EMBASE, and Web of Science databases of studies published up to September 2019 was performed. Databases were searched for prospective and retrospective cohort studies reporting on dietary phytoestrogen intake and/or blood biomarkers and the outcomes investigated.. Data were extracted from each identified study using a standardized form.. Twenty-eight articles on breast, lung, prostate, and colorectal cancer, and glioma were included for systematic review. Given the availability of studies, a quantitative meta-analysis was performed solely for breast cancer outcomes. A significant inverse association among higher dietary isoflavone intake, higher serum/plasma enterolactone concentrations, and overall mortality and cancer recurrence was found. Among other cancer types, 2 studies reported that higher serum enterolactone and higher intake of lignans were associated with cancer-specific survival for colorectal cancer and glioma, respectively.. Dietary phytoestrogens may play a role in survival from breast cancer ; evidence regarding other cancers is too limited to draw any conclusions.

Topics: 4-Butyrolactone; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diet; Eating; Female; Humans; Isoflavones; Lignans; Male; Middle Aged; Neoplasms; Phytoestrogens; Young Adult

Xenoestrogens and phytoestrogens are referred to as "foreign estrogens" that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.

Topics: Animals; Biomarkers, Tumor; Clinical Trials as Topic; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasms; Phytoestrogens; Sequence Analysis, RNA; Single-Cell Analysis; Xenograft Model Antitumor Assays

Phytoestrogens are class of natural compounds that shares structural similarity with estrogen and has the capacity to alter the fertilization in mammals. Till early 1990s, the natural phytoestrogens as well as their synthetic analogues were explored for their fertility modulating activity. During late 1990s, two findings renewed the interest on phytoestrogens as means to control hormone induced cancer: (i) revelation of overexpression of CYP1B1 in breast & ovarian cancer and (ii) protection offered by alphanapthoflavone (ANF) against hormone induced cancer. The objective of the review is to summarize the CYP1B1 inhibitory activity of phytoestrogens and their synthetic analogues reported till date. This review is an attempt to classify phytoestrogens and their synthetic analogues on their chemical architecture rather than simply by their chemical class (flavones, stilbenes etc.). This provides a broader sense to cluster many chemical classes under a particular chemical architecture/framework. Accordingly, we divided the phytoestrogen into three different classes based on two aryl groups (Ar) separated by linker (X), which may be either cyclic (c) or linear (l). The number in subscript to X denotes number of atoms: (i) Ar-cX

Topics: Animals; Antineoplastic Agents, Phytogenic; Classification; Cluster Analysis; Cytochrome P-450 CYP1B1; Enzyme Inhibitors; Humans; Molecular Mimicry; Neoplasms; Phytoestrogens

Genistein is the natural isoflavone and a phytoestrogen with a broad range of pharmacological properties, such as tyrosine and topoisomerase inhibition. It also induces apoptosis and cell proliferation inhibition, differentiates cancer cells. Added health benefits include the reduction of osteoporosis by suppressing osteoclasts and lymphocyte functions, decreased the risk of cardiovascular attacks and relieved postmenopausal problems. Genistein traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast, prostate and lung cancer. Numerous factors comprising genetic, epigenetic and transcriptomic alterations are evidenced to be responsible for breast, prostate and lung cancer. In present review, an overview on genistein, the various analytical methods and drug delivery approaches to determine genistein in the formulations are discussed. It may help to develop novel formulations with better solubility and bioavailability of genistein. The tumor cell scan may be targeted to form a stable genistein formulation.

Topics: Biological Availability; Drug Delivery Systems; Genistein; Humans; Medicine, Ayurvedic; Medicine, Chinese Traditional; Neoplasms; Phytoestrogens; Protein Kinase Inhibitors; Solubility

Great progress has been made in the fight against disease in many different fields of medicine, especially in the field of natural medicine. Phytoestrogens and related compounds play a major role in the prevention and treatment of cancer. Chemoprevention, a narrative approach for controlling cancer, involves the use of specific natural products or synthetic chemical agents to overturn, repress, or prevent pre-malignancy before the development of invasive cancer. Several natural products confer protective effects against a wide range of cancers; examples include grains, nuts, cereals, spices, fruits, vegetables, beverages, medicinal plants, herbs, and their various phytochemical constituents including phenolics, flavonoids, carotenoids, and nitrogen-containing and organosulfur compounds. Phytoestrogens and related compounds act by different mechanisms that ultimately provide benefit with minimum or no side effects and protect and treat different types of cancer, including liver, lung, colon, breast, prostate, esophagus, oral, intestinal, and many other carcinomas.

Topics: Anticarcinogenic Agents; Female; Humans; Male; Neoplasms; Phytoestrogens

ATP binding cassette (ABC) transporters are involved in drug absorption, distribution and elimination. They also mediate multidrug resistance in cancer cells. Isoflavones, such as genistein (GNT), belong to a class of naturally-occurring compounds found at high concentrations in commonly consumed soya based-foods and dietary supplements. GNT and its metabolites interact with ABC transporters as substrates, inhibitors and/or modulators of their expression. This review compiles information about regulation of ABC transporters by GNT with special emphasis on the three major groups of ABC transporters involved in excretion of endo- and xenobiotics as follows: Pglycoprotein (MDR1, ABCB1), a group of multidrug resistance associated proteins (MRPs, ABCC subfamily) and ABCG2 (BCRP), an ABC half-transporter. The impact of these regulations on potential GNT-drug interactions is further considered.

Topics: ATP-Binding Cassette Transporters; Drug Interactions; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Genistein; Humans; Neoplasms; Phytoestrogens

Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3'-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy.

Topics: Anticarcinogenic Agents; Antineoplastic Agents; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Genistein; Humans; Indoles; Kaempferols; Neoplasm Metastasis; Neoplasms; Phytoestrogens; Resveratrol; Stilbenes

The estrogenic effects of genistein, as reconfirmed by the American National Toxicology Program (USA-NTP), have led to several new clinical studies being undertaken. Here, we highlight the most relevant recent data, reporting either beneficial or adverse effects.. Phytoestrogens are natural molecules from edible plants exhibiting estrogenic activities. Post-USA-NTP studies investigated both human and animal reproductive and other physiological issues. These studies showed that estrogens can be either deleterious for reproduction and estrogen-dependent diseases, or beneficial for those with steroid deficiencies, that is more than 50. The specific outcome depends on exposure level and on the estrogenic status of the patients exposed. Recently, it was reported that, with the industrialization of soybean process, phytoestrogen exposure dramatically increased in both humans and cattle, whereas traditional Asian soy-food-processing empirically removed isoflavones. Phytoestrogen exposure has also become more widespread with the progressive internationalization of soybean use in human and cattle food.. Phytoestrogens should be considered as modern endocrine disruptors and studied as such.

Topics: Animal Feed; Animals; Cattle; Estrogens; Female; Food; Food Handling; Genistein; Glycine max; Humans; Isoflavones; Neoplasms; Phytoestrogens; Reproduction; Risk Assessment; Soy Foods; Thyroid Gland

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.

Topics: Antineoplastic Agents; Coffee; Curcumin; Diet; Epigenesis, Genetic; Folic Acid; Food; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Metabolic Syndrome; Neoplasms; Neurodegenerative Diseases; Phytoestrogens; Polyphenols; S-Adenosylmethionine; Selenium; Trace Elements; Vitamin B 12; Vitamin B Complex; Vitamins

Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided.

Topics: Amygdalin; Aristolochic Acids; Capsaicin; Cell Line, Tumor; Cycasin; Diet; Drug Screening Assays, Antitumor; Humans; Indans; Neoplasms; Phorbol Esters; Phytochemicals; Phytoestrogens; Phytotherapy; Plant Extracts; Plants; Pyrrolizidine Alkaloids; Safrole; Sesquiterpenes

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for "cancer cell specific" therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.

Topics: Apoptosis; Breast Neoplasms; Cell Cycle; Colonic Neoplasms; Dietary Supplements; Drug Delivery Systems; Female; Humans; Leukemia; Liposomes; Lung Neoplasms; Male; Neoplasms; Orphan Drug Production; Phytoestrogens; Prostatic Neoplasms; Signal Transduction; Sitosterols

Genistein is a soy derived isoflavanoid compound with multitude of health benefits. This compound is found to be a potent agent in both prophylaxis and treatment of cancer and various other chronic diseases. Ranging from its antioxidant activity to its effect on various cancer types, genistein has been a compound of interest in a number of studies carried out so far. The great interest that has focused on genistein led to the identification of numerous intracellular targets of its action in the live cells. Retardation of atherogenic activity and increasing the antioxidant defense of a cell has been attributed to genistein while as it has also been reported that genistein possesses suppressive effects on both the cell-mediated and humoral components of the adaptive immune system. At the molecular level, genistein reduces the number of developing CD4(+) and CD8(+) thymocytes suggesting a possible mechanism for genistein effects on cell-mediated immunity. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation. In addition, genistein has its prominent role in preventing the DNA damage. Apolipoprotein B secretion gets reduced when the subjects are administered with genistein. Genistein confers a better protection to ischemic conditions thereby giving a significant cardioprotection. At cellular level adipocyte differentiation is another property of genistein which makes it a better neutraceutical which can reduce the atherogenic condition and hypercholesterolemia. Expression of human endothelial nitric oxide synthase is associated with genistein supplementation. The advantage of using genistein is its multidirectional action and its lesser toxicity.

Topics: Animals; Antioxidants; Apoptosis; Genistein; Humans; Immunity, Cellular; Neoplasms; Phytoestrogens

Natural products are often used in drug development due to their ability to form unique and diverse chemical structures. Coumestans are polycyclic aromatic plant secondary metabolites containing a coumestan moiety, which consists of a benzoxole fused to a chromen-2-one to form 1-Benzoxolo[3,2-c]chromen-6-one. These natural compounds are known for large number of biological activities. Many of their biological effects can be attributed to their action as phytoestrogens and polyphenols. In the last decade, anticancer effects of these compounds have been described in vitro but there is only limited number of studies based on models in vivo. More information concerning their in vivo bioavailability, stability, metabolism, toxicity, estrogenicity, cellular targets and drug interactions is therefore needed to proceed further to clinical studies. This review focuses on coumestans exhibiting anticancer properties and summarizes mechanisms of their toxicity to cancer cells. Moreover, the possible role of coumestans in cancer prevention is discussed.

Topics: Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Coumarins; Humans; Neoplasms; Phytoestrogens; Plants

Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.

Topics: Animals; DNA Methylation; DNA Repair; Epigenesis, Genetic; Genistein; Glycine max; Histones; Humans; Isoflavones; Neoplasms; Phytoestrogens

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Beverages; Chemoprevention; Citrus; Cytoprotection; Disease Models, Animal; DNA Damage; Fruit; Humans; Neoplasms; Phytoestrogens; Randomized Controlled Trials as Topic

Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic mode of action. One mechanism relates to the different ultimate cellular effects of activation of estrogen receptor (ER) α, promoting cell proliferation, and of ERβ, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ERβ. A second mode of action includes the role of epigenetics, including effects of isoflavones on DNA methylation, histone modification and miRNA expression patterns. The overview presented reveals that we are only at the start of unraveling the complex underlying mode of action for effects of isoflavones, both beneficial or adverse, on cell proliferation and cancer risks. It is evident that whatever model system will be applied, its relevance to human tissues with respect to ERα and ERβ levels, co-repressor and co-activator characteristics as well as its relevance to human exposure regimens, needs to be considered and defined.

Topics: Animals; Apoptosis; Cell Proliferation; Co-Repressor Proteins; DNA Methylation; Estrogen Receptor alpha; Estrogen Receptor beta; Genistein; Glycine max; Histones; Humans; Isoflavones; MicroRNAs; Neoplasms; Phytoestrogens; Plant Extracts; Risk Factors

Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand. It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years. Indeed, it has been claimed that P. mirifica contains active phytoestrogens (plant substances with estrogen-like activity). Using high performance liquid chromatography, at least 17 phytoestrogens, mainly isoflavones, have been isolated. Thus, fairly considerable scientific researches, both in vitro in cell lines and in vivo in various species of animals including humans, have been conducted to date to address its estrogenic activity on the reproductive organs, bones, cardiovascular diseases and other climacteric related symptoms. The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed. In general, P. mirifica could be applicable for preventing, or as a therapeutic for, the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men. However, the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.

Topics: Animals; Antioxidants; Chromatography, High Pressure Liquid; Climacteric; Humans; Molecular Structure; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Pueraria

A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in Western countries. Hence, interest focuses on soyfoods, soy products, and soy ingredients such as isoflavones with regard to their possible beneficial effects that were observed in numerous experiments and studies. The outcomes of the studies are not always conclusive, are often contradictory depending on the experimental conditions, and are, therefore, difficult to interpret. Isoflavone research revealed not only beneficial but also adverse effects, for instance, on the reproductive system. This is also the case with tumor-promoting effects on, for example, breast tissue. Isoflavone extracts and supplements are often used for the treatment of menopausal symptoms and for the prevention of age-associated conditions such as cardiovascular diseases and osteoporosis in postmenopausal women. In relation to this, questions about the effectiveness and safety of isoflavones have to be clarified. Moreover, there are concerns about the maternal consumption of isoflavones due to the development of leukemia in infants. In contrast, men may benefit from the intake of isoflavones with regard to reducing the risk of prostate cancer. Therefore, this review examines the risks but also the benefits of isoflavones with regard to various kinds of cancer, which can be derived from animal and human studies as well as from in vitro experiments.

Topics: Animals; Anticarcinogenic Agents; Biological Availability; Carcinogenicity Tests; Carcinogens; Cardiovascular Diseases; Diet; Disease Models, Animal; Drug Combinations; Female; Glycine max; Hormone Replacement Therapy; Humans; Isoflavones; Male; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Extracts; Risk Assessment

Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside (SDG). After ingestion, SDG is converted to secoisolariciresinol, which is further metabolised to the mammalian lignans enterodiol and enterolactone. A growing body of evidence suggests that SDG metabolites may provide health benefits due to their weak oestrogenic or anti-oestrogenic effects, antioxidant activity, ability to induce phase 2 proteins and/or inhibit the activity of certain enzymes, or by mechanisms yet unidentified. Human and animal studies identify the benefits of SDG consumption. SDG metabolites may protect against CVD and the metabolic syndrome by reducing lipid and glucose concentrations, lowering blood pressure, and decreasing oxidative stress and inflammation. Flax lignans may also reduce cancer risk by preventing pre-cancerous cellular changes and by reducing angiogenesis and metastasis. Thus, dietary SDG has the potential to decrease the incidence of several chronic diseases that result in significant morbidity and mortality in industrialised countries. The available literature, though, makes it difficult to clearly identify SDG health effects because of the wide variability in study methods. However, the current evidence suggests that a dose of at least 500 mg SDG/d for approximately 8 weeks is needed to observe positive effects on cardiovascular risk factors in human patients. Flaxseed and its lignan extracts appear to be safe for most adult populations, though animal studies suggest that pregnant women should limit their exposure. The present review discusses the potential health benefits of SDG in humans, with supporting evidence from animal studies, and offers suggestions for future research.

Topics: Animals; Antioxidants; Butylene Glycols; Cardiovascular Diseases; Diabetes Mellitus; Diet; Enzyme Activators; Enzyme Inhibitors; Female; Flax; Glucosides; Humans; Lignin; Neoplasms; Phytoestrogens; Pregnancy

Isoflavones are a subgroup of phytoestrogens, natural plant substances with structure similar to 17-beta-estradiol and capable of binding to estrogen receptors (ERs). Isoflavones possess higher affinity to ERbeta than to ERalpha and may have a potency to activate both genomic and non-genomic estrogen signaling pathways. In addition, isoflavones interact with the metabolism of steroid hormones. Therefore, the actions of isoflavones are rather complex and may be related to large number of factors, which are not satisfactorily identified yet. Recently, isoflavones have come into focus of interest due to several reports about their positive effect on human health, in particular prevention of hormone-dependent cancers, cardiovascular diseases, osteoporosis, adverse menopausal manifestations and age-related cognitive decline. Isoflavones may bring new insights into the mechanisms of physiological regulations and increase the possibilities of medical interventions.

Topics: Cardiovascular Diseases; Female; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Signal Transduction

Cancer is a leading cause of death worldwide, and the numbers of new cancer cases are expected to continue to rise. The main goals of cancer therapy include removing the primary tumor, preventing the spread of distant metastases, and improving survival and quality of life for the patients. To attain these goals of cancer therapy, the combination of different chemotherapeutics, as opposed to the conventional single-agent treatment, is an emerging area of research. Given the potential risks of drug toxicity in such treatment, the focus is to have a second compound that increases the anticancer potential of the primary agent but which reduces toxicity. There is an ever growing interest in treatment with natural compounds, such as plant phytoestrogens, as an adjuvant cancer therapy along with conventional cancer therapy. The question remains whether or not adding these compounds to the cancer therapy regimen as a second agent would be beneficial, and if they are safe to be used among cancer patients. The current literature suggests that phytoestrogen treatment is capable of inducing G2/M cell cycle arrest in a number of cancer cell lines, as well as upregulating cell cycle inhibitory molecules. Phytoestrogen therapy has been shown to inhibit inflammation, angiogenesis and metastases in various IN VIVO tumor models, and pronounced benefits have been observed when combined with radiation therapy. The lack of side effects from phase I and II clinical trials of phytoestrogens in cancer therapy points towards their safety, but to further understand their added benefit clinical studies with large sample sizes are required. We have reviewed the recent research studies in these areas in an attempt to find evidence for their role in cancer therapy as well as safety.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Cycle; Chemotherapy, Adjuvant; Humans; Inflammation; Isoflavones; Lignans; Mice; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Phytoestrogens; Randomized Controlled Trials as Topic

Resveratrol is a phytoalexin, highly abundant in skins of red grapes and moderately abundant in peanuts and blueberries. Originally a constituent of oriental medicines, it has lately been rediscovered for a plethora of beneficial properties such as anti-cancer, anti-aging, antiviral, cardiovascular and neuroprotective effects, thereby making it one of the most sought after phytochemicals for supplementing human diet. Studies done in various laboratories have shown its modulatory effects on multitudes of cell signaling and gene expression pathways. Although most of its effects have been observed in cultured cells, quite a few have also been validated in whole animals as well. It is thus necessary to have a comprehensive look at all those effects of resveratrol in an organismal context. The following review summarizes the effects of resveratrol in the context of chemoprevention.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cardiovascular Diseases; Drug Evaluation, Preclinical; Gene Expression Regulation; Humans; Neoplasms; Neoplasms, Hormone-Dependent; Phytoestrogens; Resveratrol; Signal Transduction; Stilbenes

GPR30, now named GPER1 (G protein-coupled estrogen receptor1) or GPER here, was first identified as an orphan 7-transmembrane G protein-coupled receptor by multiple laboratories using either homology cloning or differential expression and subsequently shown to be required for estrogen-mediated signaling in certain cancer cells. The actions of estrogen are extensive in the body and are thought to be mediated predominantly by classical nuclear estrogen receptors that act as transcription factors/regulators. Nevertheless, certain aspects of estrogen function remain incompatible with the generally accepted mechanisms of classical estrogen receptor action. Many recent studies have revealed that GPER contributes to some of the actions of estrogen, including rapid signaling events and rapid transcriptional activation. With the introduction of GPER-selective ligands and GPER knockout mice, the functions of GPER are becoming more clearly defined. In many cases, there appears to be a complex interplay between the two receptor systems, suggesting that estrogen-mediated physiological responses may be mediated by either receptor or a combination of both receptor types, with important medical implications.

Topics: Animals; Estrogen Receptor Modulators; Estrogens; Female; Gene Expression Regulation; Humans; Ligands; Male; Neoplasms; Phytoestrogens; Pregnancy; Receptors, Estrogen; Receptors, G-Protein-Coupled; Selective Estrogen Receptor Modulators; Signal Transduction

Together with the estrogen receptor (ER) alpha, estrogen receptor beta (ER beta ) mediates many of the physiological effects of estrogens. As ER beta is crucially involved in a variety of important physiological processes, its activity should be tightly regulated. ER beta regulation is achieved by hormone binding as well as by posttranslational modifications of the receptor. Furthermore, ER beta expression levels are under circadian control and can be regulated by DNA methylation of the ER beta promoter region. There are also a number of factors that can interfere with ER beta activity, such as phytoestrogens, endocrine disruptive chemicals, and growth factors. In this article, we outline different mechanisms of ER beta regulation and how they are implicated in various diseases. We also discuss how these insights might help to specifically target ER beta in drug design.

Topics: Alternative Splicing; DNA Methylation; Estrogen Receptor beta; Gene Expression Regulation, Neoplastic; Humans; Models, Biological; Neoplasms; Phytoestrogens; Protein Binding; Protein Processing, Post-Translational

Lignans are diphenolic compounds widely distributed in the plant kingdom. They are mainly localised in lignified tissues, seeds and roots. These molecules are involved in plant defence mechanisms, but are also interesting for human health. Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers. In vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action. The most studied lignan, podophyllotoxin, and its semi-synthetic derivatives (etoposide, teniposide, etoposide phosphate), are particularly interesting at a curative level due to their cytotoxic properties. These semi-synthetic derivatives are used in chemotherapy of lung cancer for example. However, the extensive use of these anticancer drugs will lead to the problem of podophyllotoxin supply. This molecule is currently extracted from the rhizomes and roots of an Indian species Podophyllum hexandrum which has subsequently become endangered. Strategies are investigated to obtain economically viable alternative sources of Podophyllotoxin from plants and in vitro cultures of several species. Among them, north american Podophyllum peltatum, Linum wild species, Hyptis, Anthriscus, Juniperus or Dysosma species which accumulate Podophyllotoxin or closely related derivatives, are good candidates. double dagger.

Topics: Anticarcinogenic Agents; Antineoplastic Agents; Humans; Lignans; Neoplasms; Phytoestrogens; Podophyllotoxin

In Europe, endocrine disruptors (EDs) have been defined as substances foreign to the body that have deleterious effects on the individuals or their descendants, due to changes in endocrine function. In the United States, EDs have been described as exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of the natural ligands responsible for maintaining homeostasis and regulating body development. These two definitions are complementary, but both indicate that the effects induced by EDs probably involve mechanisms relating in some way to hormonal homeostasis and action. EDs are generally described as substances with anti-oestrogenic, oestrogenic, anti-androgenic or androgenic effects. More recently, other targets have been evidenced such as the thyroid and immune system. Many different EDs are present in the various compartments of the environment (air, water and land) and in foods (of plant and animal origin). They may originate from food packaging, combustion products, plant health treatments, detergents and the chemical industry in general. In addition to the potential effects of these compounds on adults, the sensitivity of embryos and fetuses to many of the xenobiotic compounds likely to cross the placenta has raised considerable concern and led to major research efforts. With the exception of the clearly established links between diethylstilbestrol, reproductive health abnormalities and cancers, very little is known for certain about the effects of EDs on human health. Given the lack of available data, current concerns about the possible involvement of EDs in the increase in the incidence of breast cancer, and possibly of endometriosis and early puberty in girls, remain hypothetical. Conversely, the deterioration in male reproductive health is at the heart of preoccupations and progress in analyses of the relationship between EDs and human health. This literature review aims to describe the current state of knowledge about endocrine disruption, focusing in particular on the problem of food contaminants.

Topics: Abnormalities, Drug-Induced; Animals; Benzhydryl Compounds; Diethylstilbestrol; Endocrine Disruptors; Endocrine System Diseases; Environmental Health; Environmental Pollutants; Female; Fetus; Food Contamination; Gonadal Dysgenesis; Homeostasis; Humans; Industrial Waste; Infertility, Male; Male; Mammary Neoplasms, Experimental; Neoplasms; Pesticide Residues; Phenols; Phthalic Acids; Phytoestrogens; Plastics; Pregnancy; Prenatal Exposure Delayed Effects; Rats

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 non-estrogen 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.

Topics: Humans; Neoplasms; Phytoestrogens; Phytotherapy

Supplementation with the crucifer-derived phytochemicals indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) has been an area of active interest due to their role in estrogen metabolism. This review addresses the debate about which cruciferous compound to use clinically by evaluating their efficacy and safety. Significantly more clinical trials are available for I3C than for DIM. I3C leads to beneficial shifts in hormone markers, and limited evidence suggests that DIM may result in a similar effect. More research in humans is needed to further address whether DIM poses any safety risk. Current data do not suggest that DIM provides enhanced clinical benefits over I3C.

Topics: Anticarcinogenic Agents; Brassicaceae; Consumer Product Safety; Humans; Indoles; Neoplasms; Phytoestrogens; Risk Factors; Vegetables

In recent years, isoflavones have increased in popularity as an alternative to estrogen therapy, particularly after the Women's Health Initiative demonstrated an increased risk of breast cancer, stroke, and heart attacks in response to estrogen and progesterone intervention. Isoflavones are heterocyclic phenols with structural similarity to estradiol-17beta and selective estrogen receptor modulators. Actions at the cellular level depend on the target tissue, receptor status of the tissue, and the level of endogenous estrogen. Clinical studies of soy-based diets evaluating the relation between soy consumption and serum lipid concentrations revealed that soy consumption significantly decreased total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. Epidemiological studies suggest a protective effect of soy protein on breast tissue as evidenced by the lower rates of breast cancer in East Asian countries where soy is a predominant part of the diet. Soy products also alleviate menopausal symptoms by reducing hot flashes. However, whether these biological effects of soy products originated from isoflavones is not clear. Furthermore, data available from human studies on the effect of isoflavones on osteoporosis are limited, and additional studies are needed to support a role in osteoporosis prevention. To date, no adverse effects of short- or long-term use of soy proteins are known in humans, and the only adverse effects known are those reported in animals. In conclusion, isoflavones are biologically active compounds, and current data are insufficient to draw definitive conclusions regarding the use of isoflavones as an alternative to estrogen for hormone replacement in postmenopausal women. Large, long-term intervention studies examining adverse effects and disease outcomes are needed before definitive conclusion can be drawn.

Topics: Cardiovascular Diseases; Diet; Female; Flavonoids; Glycine max; Health Promotion; Humans; Infant Formula; Isoflavones; Menopause; Neoplasms; Phytoestrogens

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Topics: Anticarcinogenic Agents; Breast Neoplasms; Cardiovascular Diseases; Female; Genistein; Glycine max; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Postmenopause; Randomized Controlled Trials as Topic

The use of complementary and alternative medicine (CAM) is increasing rapidly in developed countries, which is already in use as traditional medicines in various Asian countries. The Indian system of medicine, named as Ayurveda has an edge in this field. Many plant products are in use as herbal medicine, as food supplement or as spices, in every day cooking. Some of them have been well studied in various experimental models of cancer, both in vivo and in vitro models. They have shown significant inhibition of cell proliferation. Some of them are in the phase of clinical trial or already available as food supplement. Cancer patients are specially exploring the use of CAM, because of the high risk of mortality and long-term morbidity associated with surgical procedures of cancer management and high side effects of chemotherapy. This paper reviews different class of phytomedicines, used in Indian system of medicine, and also in Europe, which have shown positive results in preventing cancer progression. It also covers the role of vitamins, minerals, dietary fat in relation to cancer control. The mechanisms of action of these phytomolecules have also been discussed.

Topics: Antioxidants; Capsaicin; Carotenoids; Catechin; Catechols; Complementary Therapies; Curcumin; Fatty Alcohols; Flavones; Genistein; Herbal Medicine; Humans; Isoflavones; Lycopene; Minerals; Neoplasms; Phytoestrogens; Phytotherapy; Plant Preparations; Vitamins

A wide array of antioxidative and anti-inflammatory substances derived from edible plants have been reported to possess chemopreventive and chemoprotective activities. Among the most extensively investigated and well-defined dietary chemopreventives are epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea and genistein, a major pharmacologically active isoflavone widely present in soy products. Multiple lines evidence from epidemiologic studies indicate that frequent consumption of green tea is inversely associated with the risk of several types of human cancer, and studies with animal and in vitro cell culture models have revealed EGCG as a major chemopreventive ingredient of green tea. The lower frequencies of breast and prostate cancer in Asian population in general, compared to those in Western societies have been attributed to their consumption of relatively large amounts of soy products. Genistein, as a principal chemopreventive components of soy, exerts a wide array of chemopreventive activities in each stage of multistep carcinogenesis. The purpose of this review is to provide perspectives on the molecular basis of chemopreventive activities of EGCG and geneistein as representative functional food phytochemicals with emphasis on their ability to control intracellular signaling cascades responsible for regulating cell growth and differentiation.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Catechin; Cell Cycle; Diet; Epidemiologic Methods; Estrogen Antagonists; Food; Genistein; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations

To review 32 herbs and natural products that show potential to increase cancer growth or recurrence or to interfere with cancer treatments.. Natural Medicines Comprehensive Database and Lawrence Review of Natural Products Monograph System.. Early evidence shows that patients who have or have had cancer should avoid 32 herbs and natural products. Some herbs and natural products have estrogenic effects that enable these products to compete with hormone cancer therapies, whereas others interfere with chemotherapy treatment or may induce recurrence of cancer.. Healthcare professionals can be resources for patients who have cancer, helping them to avoid or identify products that may induce cancer growth or interfere with cancer treatment.. The information in this article is designed to provide quick access for healthcare professionals working in clinical oncology.

Topics: Animals; Antineoplastic Agents; Biological Products; Contraindications; Disease Progression; Drug Interactions; Estrogens; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplasms; Neoplasms, Hormone-Dependent; Oxidation-Reduction; Phytoestrogens; Phytotherapy; Plants, Medicinal; Self Medication

The aim of this article was to present a simple classification of phytoestrogens, their approximate content in food products as well as their synthesis, biotransformation and activity in human organism. Having various mechanisms of action, phytoestrogens display both beneficial and adverse effects on physiological processes. Several positive health effects have been associated with phytoestrogens, such as a protective role against the development of cancers, proestrogenic effects (particularly with postmenopausal women) and beneficial influence on cardiovascular and osseous systems. Adverse effects of phytoestrogens have been observed in fetuses and young specimens. Limited studies have displayed disorders in morphology and physiology of the male reproductive system. High plasma phytoestrogens level inhibits a cellular activity of some enzymes, e.g. enzymes involved in the synthesis of steroid hormones. Direct contact with exogenous, environmental estrogens depends on human diet and it can be variable in different populations.

Topics: Cardiovascular Diseases; Female; Fertility; Humans; Male; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations

Soy infant formula contains high levels of the isoflavones, genistein and daidzein, which are commonly referred to as phytoestrogens. These are non-steroidal chemicals with structural similarities to estrogen. Infants consuming soy formula have high levels of circulating isoflavones. These are an order of magnitude greater than the levels of isoflavones which have been shown to produce physiological effects in adult women consuming a high soy diet. There is conflicting evidence about the risks and benefits of soy phytoestrogens, with research presenting a contradictory picture. Some reviewers suggest that early exposure to soy may prevent cancer and heart disease. However, there is very little research on the effects of consumption of soy phytoestrogens by human neonates. Against this generally positive view there is an increasing number of recent reports that suggest that in experimental animals, phytoestrogens have adverse effects with respect to carcinogenesis, reproductive function, immune function, and thyroid disease. Despite the absence of adequate scientific research that quantifies the level of risk to infants, most would argue for a precautionary approach to be taken in situations where there are potential developmental effects from the consumption of pharmacologically active compounds in infancy and childhood.

Topics: Endocrine Glands; Humans; Infant; Infant Formula; Neoplasms; Phytoestrogens; Reproduction; Risk Assessment; Soy Foods

This Review covers the sources and the main effects on human health of well-known micronutrients such as minerals and vitamins and also of microconstituents contained in the Mediterranean diet. Vitamins were first identified because of deficiency diseases still present in certain parts of the world. Hydrosoluble vitamins, among them folic acid and vitamin C, also play a role in chronic degenerative diseases, not only the main cause of mortality in the Western world but also increasingly common in developing countries. Hydrosoluble vitamins are well represented in the Mediterranean diet, more so than vitamin A, a liposoluble vitamin obtained primarily from animal foods. Vitamin E is important for antioxidant and cellular functions. The Mediterranean diet is also rich in provitamins A, such as alpha- and beta-carotene and beta-cryptoxanthine. Microconstituents are non-nutritional compounds known to protect plants and more recently suspected to have a protective effect in humans. They play a role in the antioxidant defense of the organism, but their effect on various enzyme activities appears even more promising and is still under investigation. It is nevertheless difficult to isolate the effect of the numerous biofactors present in the Mediterranean diet from the foods themselves, especially because of the possible synergy between the various biofactors.

Topics: Allyl Compounds; Cardiovascular Diseases; Carotenoids; Diet, Mediterranean; Disulfides; Glucosinolates; Humans; Isoflavones; Micronutrients; Minerals; Models, Biological; Neoplasms; Phenols; Phytoestrogens; Plant Preparations; Terpenes; Vitamins

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, le

Topics: Antioxidants; Cardiovascular Diseases; Carotenoids; Chronic Disease; Dietary Fiber; Estrogens, Non-Steroidal; Food; Humans; Isoflavones; Isothiocyanates; Lycopene; Monoterpenes; Neoplasms; Olive Oil; Phenols; Phytoestrogens; Phytosterols; Plant Oils; Plant Preparations; Resveratrol; Stilbenes; Tea

Estrogens are known for their proliferative effects on estrogen-sensitive tissues resulting in tumorigenesis. Results of experiments in multiple laboratories over the last 20 years have shown that a large part of the cancer-inducing effect of estrogen involves the formation of agonistic metabolites of estrogen, especially 16-alpha-hydroxyestrone. Other metabolites, such as 2-hydroxyestrone and 2-hydroxyestradiol, offer protection against the estrogen-agonist effects of 16-alpha-hydroxyestrone. An ELISA method for measuring 2- and 16-alpha-hydroxylated estrogen (OHE) metabolites in urine is available and the ratio of urinary 2-OHE/16-alpha-OHE (2/16-alpha ratio) is a useful biomarker for estrogen-related cancer risk. The CYP1A1 enzyme that catalyzes 2-hydroxyestrone (2-OHE1) formation is inducible by dietary modification and supplementation with the active components of cruciferous vegetables, indole-3-carbinol (I-3-C), or diindolylmethane (DIM). Other dietary components, especially omega-3 polyunsaturated fatty acids and lignans in foods like flax seed, also exert favorable effects on estrogen metabolism. Thus, there appear to be effective dietary means for reducing cancer risk by improving estrogen metabolism. This review presents the accumulated evidence to help clinicians evaluate the merit of using tests that measure estrogen metabolites and using interventions to modify estrogen metabolism.

Topics: Breast Neoplasms; Estradiol; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Hydroxylation; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Postmenopause; Uterine Neoplasms; Vegetables

Despite the benefits of conventional hormone replacement therapy, some women are not candidates for this treatment and many others choose not to take it. As a result, there is growing interest among patients about natural alternatives. There is some evidence that phytoestrogens may offer protection against a wide range of human conditions, including breast cancer, cardiovascular disease, brain dysfunction, osteoporosis, and menopausal symptoms. The literature on the possible health benefits of phytoestrogens has expanded exponentially since the 1980s, mainly in response to funding initiatives by the U.S. government and soybean industries, and more lately by European and UK Ministries of Food. The physiological effects of phytoestrogens also have created a marketing opportunity that has been used by industry, particularly in soybean-producing countries such as the U.S. and Australia. Nevertheless, clinical applications for phytoestrogens are still in their infancy, and more interventional trials are required to reach definitive conclusions regarding their efficacy and safety, although they appear to represent a promising group of compounds, which may be useful in the future for the treatment of the menopausal syndrome. Also, the lack of clinical data presently available must signal caution in relation to the possible risk of adverse effects.. Obstetricians and Gynecologists, Family Physicians.. After completion of this article, the reader will be able to identify the various types of phytoestrogens, list the sources of phytoestrogens, and summarize the various effects of phytoestrogens.

Topics: Cardiovascular Diseases; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Neoplasms; Osteoporosis; Phytoestrogens; Plant Preparations; Postmenopause; Risk Factors

Genistein (4',5,7-trihydroxyisoflavone) is a common precursor in the biosynthesis of antimicrobial phytoalexins and phytoanticipins in legumes, and an important nutraceutical molecule found in soybean seeds. Genistein is a phytoestrogen with a wide variety of pharmacological effects in animal cells, including tyrosine kinase inhibition, and dietary genistein ingestion has been linked, through epidemiological and animal model studies, with a range of potential health beneficial effects. These include chemoprevention of breast and prostate cancers, cardiovascular disease and post-menopausal ailments. In spite of an extensive literature on the effects of dietary genistein, questions still exist as to its potential overall benefits as a component of the human diet. Genistein can be synthesized chemically via the deoxybenzoin or chalcone route. Genistein is synthesized in plants from the flavanone naringenin by a novel ring migration reaction catalyzed by the cytochrome P450 enzyme isoflavone synthase (IFS). IFS genes have recently been cloned from a number of plant species, and production of genistein can be now achieved in non-legumes by recombinant DNA approaches.

Topics: Biological Availability; Chemoprevention; Estrogens, Non-Steroidal; Genistein; Glycine max; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Genetically Modified; Postmenopause

Phyto-oestrogens have been suggested to have a preventive effect against various cancers. This review includes a discussion of the consumption of phyto-oestrogen-rich foods such as soy, a source of isoflavones, and whole grain products, which contain lignans, and their role in the prevention of breast, prostate, and colon cancer. In women, a soy-containing diet is only slightly protective against breast cancer, if at all, but is more likely to be beneficial if initiated before puberty or during adolescence. These findings are supported by conclusions of studies of immigrants and other epidemiological studies. However, in one case-control study and one prospective study, a low-lignan diet increased the risk of breast cancer. Experimental evidence also exists for an inhibitory effect of soy and rye bran on prostate-cancer growth and for rye bran or isolated lignans on colon cancer. Whether these observed protective effects are caused by the presence of dietary phyto-oestrogens, or whether they are merely indicators of a healthy diet in general, has not been established.

Topics: 4-Butyrolactone; Animals; Breast Neoplasms; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Tumor Cells, Cultured

Topics: alpha-Amylases; Animals; Estrogens, Non-Steroidal; Glycine max; Humans; Isoflavones; Neoplasms; Phytic Acid; Phytoestrogens; Plant Preparations; Plant Proteins; Saponins; Trypsin Inhibitors

Topics: Breast Neoplasms; Endometrial Neoplasms; Epidemiologic Studies; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lung Neoplasms; Male; Neoplasms; Neoplasms, Hormone-Dependent; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Risk Factors; Stomach Neoplasms

Dietary guidance recommends consumption of whole grains for the prevention of cancer. Epidemiologic studies find that whole grains are protective against cancer, especially gastrointestinal cancers such as gastric and colonic, and hormonally-dependent cancers including breast and prostate. Four potential mechanisms for the protectiveness of whole grains against cancer are described. First, whole grains are concentrated sources of dietary fiber, resistant starch, and oligosaccharides, fermentable carbohydrates thought to protect against cancer. Fermentation of carbohydrates in the colon results in production of short chain fatty acids that lower colonic pH and serve as an energy source for the colonocytes. Secondly, whole grains are rich in antioxidants, including trace minerals and phenolic compounds, and antioxidants have been proposed to be important in cancer prevention. Thirdly, whole grains are significant sources of phytoestrogens that have hormonal effects related to cancer protection. Phytoestrogens are thought to be particularly important in the prevention of hormonally-dependent cancers such as breast and prostate. Finally, whole grains mediate glucose response, which has been proposed to protect against colon and breast cancer.

Topics: Antioxidants; Diet; Digestive System; Edible Grain; Estrogens, Non-Steroidal; Fermentation; Humans; Insulin; Isoflavones; Neoplasms; Obesity; Phytoestrogens; Plant Preparations; Risk Factors

To present the currently available evidence on the cardiovascular benefits and risks associated with phyto-oestrogens. DATA-SYNTHESIS: Medline search from 1966-1999 updated with cross-check of references of papers with keywords such as phyto-oestrogens, isoflavones, lignans, genistein, daidzein, enterolactone, enterodiol, cardiovascular disease, cardiovascular disease risk factors.. Phyto-oestrogens are plant chemicals divided into three main classes: isoflavones, coumestans, and lignans that display oestrogen-like activity due to their ability to bind to the oestrogen receptor. They are found in grains, beans, green vegetables, fruits, nuts, and grasses. Isoflavones are primarily found in soybeans and soy foods. For epidemiological studies of the relation between phyto-oestrogen intake and disease parameters, intake is estimated with several measures, such as biomarkers (concentrations in urine or blood) or dietary questionnaires, though the optimal method is not yet clear. Phyto-oestrogens are considered to act as selective oestrogen receptor modulators (SERM), exerting both oestrogen agonist and antagonist action. Supplementation with isolated soy protein containing the isoflavones genistein and daidzein reduces serum total and LDL-cholesterol and triglycerides in animals and in humans. Vascular reactivity might be improved by supplementation with isolated soy protein or isoflavones isolated from red clover. Studies on atherosclerosis in animals indicate a potential for risk reduction. Evidence in humans is still scanty. The little we know of the effects of regular dietary phyto-oestrogen intake comes from studies in which phyto-oestrogens were added to the usual diet. Most supplementation studies have been conducted with soy isoflavones, whereas the importance of lignans has not been determined, though they could be more important sources than isoflavones in Western populations. Research has been focused on risk factors. Studies of clinically manifest endpoints are urgently needed.

Topics: Animals; Arteriosclerosis; Bone Density; Cardiovascular Diseases; Diet; Dietary Supplements; Estrogens, Non-Steroidal; Humans; Isoflavones; MEDLINE; Models, Animal; Neoplasms; Phytoestrogens; Plant Preparations; Risk Factors; Soybean Proteins

Epidemiological studies revealed that foodstuffs, in particular, soy foods containing isoflavonoid phytoestrogens may reduce the risk of some hormone-dependent disease such as not only postmenopausal symptoms but also certain(breast, prostate and colon) cancers and cardiovascular disease. This review introduces the metabolism of soybean isoflavonoids by human intestinal bacteria and the binding and gene-expression activity of the metabolites towards the human estrogen receptor(hER) alpha and beta. The dietary isoflavones(daidzin and genistin) in soybean were metabolized to equol and dihydrogenistein via daidzein and genistein, respectively. The metabolites bind more strongly to hER beta than hER alpha. The binding affinity of genistein is comparable that of 17 beta-estradiol. Equol induces transcription most strongly both with hER beta and hER alpha.

Topics: Bacteria; Chromans; Digestive System; Equol; Estrogens, Non-Steroidal; Female; Gene Expression; Genistein; Humans; Isoflavones; Myocardial Ischemia; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Receptors, Estrogen

The bioavailability in human subjects of non-nutrient plant factors, including dietary flavonoids and phyto-oestrogens, is of great importance relative to their reported health protective effects. These effects include protection against heart disease, and also in the case of the phyto-oestrogens, hormone-dependent cancers. Epidemiological studies have shown flavonoid intake (mostly quercetin) to be inversely associated with mortality from CHD. Quercetin is a potent antioxidant in vitro, and protection against the oxidative damage to LDL implicated in atherogenesis has been suggested as a possible mechanism. Human subjects can absorb significant amounts of quercetin (particularly in the glucoside form) and it would appear to be sufficiently bioavailable to act as an antioxidant in vivo; however, following our recent study (J O'Reilly, TAB Sanders and H Wiseman, unpublished results), it is currently less clear whether quercetin really can act as an antioxidant in vivo. The isoflavone phyto-oestrogens genistein and daidzein are much less effective antioxidants than quercetin in vitro, however, they are well-absorbed by human subjects and appear to be sufficiently bioavailable to act as antioxidants in vivo. In our recent study (O'Reilly et al. 1998) lower plasma isoprostane concentrations and increased resistance of LDL to oxidation were observed following the high-isoflavone dietary phase compared with the low-isoflavone dietary phase. Considerable inter-individual variation in isoflavone metabolite excretion has been observed, in particular the production of equol (the gut bacterial metabolite of daidzein; a more potent antioxidant and more oestrogenic than daidzein), and this appears to be influenced by habitual diet. Further studies on the bioavailability of these non-nutrient plant factors and related influencing factors are clearly still required.

Topics: Biological Availability; Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Flavonoids; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Quercetin

These results, describing antitumor activity of some of the phytochemicals that have been actively studied, suggest that dietary changes could play a role in decreasing the incidence of a variety of tumors. 13C and the other compounds discussed may well be only prototypes for other as yet unexplored phytochemicals present in the diet. There have been no attempts to explore the possibilities of synergistic action among the various phytochemicals, 13C, limonene, curcumin, epigallocatechin gallate, sulforaphene, or genistein. Mixtures of these compounds might well show potency at lower doses for each of the compounds and show even greater promise than that already demonstrated.

Topics: Anticarcinogenic Agents; Catechin; Estrogens, Non-Steroidal; Female; Humans; Indoles; Isoflavones; Isothiocyanates; Male; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible; Risk Factors; Sulfoxides; Thiocyanates

We have reviewed the literature regarding the food sources, potency, population intakes, and known biological effects of phytoestrogens in humans using MEDLINE data base from the years 1975-1996. Over 600 articles pertinent to the metabolism of phytoestrogens, including female reproduction (in particular menstruation and menopause), cardiovascular disease, osteoporosis, and cancer were assessed including relevant case control or cohort studies, as well as randomized trials and review articles. Epidemiological studies regarding human data were included, as well as human cell line and animal studies when there were no relevant human data available. We conclude that phytoestrogens exhibit physiological effects in humans. Mild estrogenic changes occur in postmenopausal women. Benefits are seen regarding hypercholesterolaemia. Epidemiological, animal, and in vitro data encourage further assessment of the role of phytoestrogens in cancer prevention.

Topics: Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; MEDLINE; Menopause; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible

Topics: Animals; Anticarcinogenic Agents; Bacteria; Estrogens, Non-Steroidal; Humans; Intestines; Isoflavones; Neoplasms; Nutritional Physiological Phenomena; Phytoestrogens; Plant Preparations

The community and the scientific world are developing a great interest in phytoestrogens. This article reviews the current literature regarding the effects of phytoestrogen consumption in humans in relation to menopause, cardiovascular disease and cancer. Studies that adhere to scientific scrutiny such as randomised double blind studies are assessed.

Topics: Cardiovascular Diseases; Climacteric; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible

Phyto-oestrogens have emerged from their esoteric role in animal husbandry following the hypothesis that the human Western diet is relatively deficient in these substances compared with societies where large amounts of plant foods and legumes are eaten. Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers, cardiovascular disease, brain function, alcohol abuse, osteoporosis and menopausal symptoms. Of the two main classes of these weak oestrogens, the isoflavones are under intensive investigation due to their high levels in soyabean. Like the 'anti-oestrogen' Tamoxifen, these seem to have oestrogenic effects in human subjects in the cardiovascular system and bone. Although previously only available from food, isoflavones are now being marketed in health-food supplements or drinks, and tablets may soon be available over the counter as 'natural' hormone-replacement therapy. In cancer, anti-oestrogenic effects are thought to be important, although genistein especially has been shown to induce wide-ranging anti-cancer effects in cell lines independent of any hormone-related influence. There are few indications of harmful effects at present, although possible proliferative effects have been reported. In infants, the effects of high levels in soya milk formulas are uncertain. The second group, lignans, have been less investigated despite their known antioestrogenic effects and more widespread occurrence in foods. Investigation of the possible benefits of phyto-oestrogens is hampered by lack of analytical standards and, hence, inadequate methods for the measurement of low levels in most foods. This problem may prove to be a major dilemma for regulatory authorities, clinicians and others wishing to advise the general public on whether these compounds really do have the health benefits attributed to them.

Topics: Coronary Disease; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Male; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Factors

Phytoestrogens are naturally occurring plant compounds which have oestrogenic and/or anti-oestrogenic activity. They are present in many human foodstuffs including beans, sprouts, cabbage, spinach, soyabean, grains and hops. The main classes are the isoflavones, coumestans and lignans. This review assesses the evidence that these substances may have adverse and/or beneficial impacts on the risk of several hormone-dependent diseases in humans. Evidence from studies of various animal species has demonstrated that ingestion of high levels of phytoestrogens can produce adverse effects on reproductive endpoints including fertility. Studies in laboratory animals have also shown that exposure to high doses of phytoestrogens during development can adversely affect brain differentiation and reproductive development in rodents, but may also have possible beneficial effects. In humans, there is a lack of information concerning the possible effects of high doses of phytoestrogens in infants and this should be addressed as a matter of priority so that any risks (or benefits) can be established. In adults, no current data exist to suggest that consumption of phytoestrogens at the levels normally encountered in the diet is likely to be harmful. Epidemiological studies suggest that foodstuffs containing phytoestrogens may have a beneficial role in protecting against a number of chronic diseases and conditions. For cancer of the prostate, colon, rectum, stomach and lung, the evidence is most consistent for a protective effect resulting from a high intake of grains, legumes, fruits and vegetables; it is not possible to identify particular food types or components that may be responsible. Dietary intervention studies indicate that in women soya and linseed may have beneficial effects on the risk of breast cancer and may help to alleviate postmenopausal symptoms. For osteoporosis, tentative evidence suggests phytoestrogens may have similar effects in maintaining bone density to those of the related pharmaceutical compound ipriflavone. Soya also appears to have beneficial effects on blood lipids which may help to reduce the risk of cardiovascular disease and atherosclerosis. Generally, however, little evidence exists to link these effects directly to phytoestrogens; many other components of soya and linseed are biologically active in various experimental systems and may be responsible for the observed effects in humans. It is concluded that dietary phytoestrogens may have a r

Topics: Adult; Animals; Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Fertility; Humans; Infant; Isoflavones; Male; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations; Plants

The consumption of a plant-based diet can prevent the development and progression of chronic diseases associated with extensive neovascularization, including the progression and growth of solid malignant tumours. We have previously shown that the plant-derived isoflavonoid genistein is a potent inhibitor of cell proliferation and in vitro angiogenesis. Moreover, the concentration of genistein in the urine of subjects consuming a plant-based diet is 30-fold higher than that in subjects consuming a traditional Western diet. We have also reported that certain structurally related flavonoids are more potent inhibitors than genistein. Indeed, 3-hydroxyflavone, 3',4'-dihydroxyflavone, 2',3'-dihydroxyflavone, fisetin, apigenin and luteolin inhibit the proliferation of normal and tumour cells as well as in vitro angiogenesis at half-maximal concentrations in the lower micromolar range. The wide distribution of isoflavonoids and flavonoids in the plant kingdom, together with their anti-angiogenic and anti-mitotic properties, suggest that these phytoestrogens may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumours.

Topics: Cell Division; Endothelium, Vascular; Estrogens, Non-Steroidal; Genistein; Humans; In Vitro Techniques; Isoflavones; Neoplasms; Neovascularization, Pathologic; Phytoestrogens; Plant Preparations

Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable.

Topics: Acute Disease; Antioxidants; Cardiovascular Diseases; Dietary Fiber; Eating; Edible Grain; Estrogens, Non-Steroidal; Humans; Intestine, Large; Isoflavones; Lignans; Models, Biological; Neoplasms; Nutritional Requirements; Phytoestrogens; Plant Preparations; Risk Factors; Starch

The evidence that natural isoflavones protect against several chronic diseases is both observational and experimental. In humans, epidemiologic findings clearly show a higher incidence of some common types of cancer (i.e., breast, prostate, and colon) and of coronary heart diseases in Western populations exposed to limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet. Further evidence for cancer and cardiac protection and antiatherogenic effects resulting from soybean isoflavones administration has been noted in various experimental animal models. Isoflavones may also prevent postmenopausal bone loss and osteoporosis. In fact, genistein has been reported to be as active as estrogens in maintaining bone mass in ovariectomized rats. Moreover, the synthetic isoflavone derivative ipriflavone is able to reduce bone loss in various types of animal models of experimental osteoporosis providing a rationale on its use in the prevention and treatment of postmenopausal and senile osteoporosis in humans. The mechanism through which isoflavones may exert the above-mentioned effects seems to depend, at least in part, on their mixed estrogen agonist-antagonist properties. An alternative hypothetical mechanism could derive from other biochemical actions of isoflavones such as inhibition of enzymatic activity, in particular protein kinases, or activation of an "orphan" receptor distinct from the estrogen type I receptor.

Topics: Animals; Coronary Disease; Diet; Disease Models, Animal; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Receptors, Estrogen

To review the sources, metabolism, potencies, and clinical effects of phytoestrogens on humans.. The MEDLINE data base for the years 1980-1995 and reference lists of published articles were searched for relevant English-language articles concerning phytoestrogens, soy products, and diets with high-phytoestrogen content.. We identified 861 articles as being relevant. Human cell line studies, human epidemiologic studies (case-control or cohort), randomized trials, and review articles were included. Animal studies regarding phytoestrogens were included when no human data were available concerning an important clinical area.. Included were studies containing information considered pertinent to clinical practice in the areas of growth and development, menopause, cancer, and cardiovascular disease. When findings varied, those presented in this study reflect consensus. All studies concurred that phytoestrogens are biologically active in humans or animals. These compounds inhibit the growth of different cancer cell lines in cell culture and animal models. Human epidemiologic evidence supports the hypothesis that phytoestrogens inhibit cancer formation and growth in humans. Foods containing phytoestrogens reduce cholesterol levels in humans, and cell line, animal, and human data show benefit in treating osteoporosis.. This review suggests that phytoestrogens are among the dietary factors affording protection against cancer and heart disease in vegetarians. With this epidemiologic and cell line evidence, intervention studies are now an appropriate consideration to assess the clinical effects of phytoestrogens because of the potentially important health benefits associated with the consumption of foods containing these compounds.

Topics: Animals; Cardiovascular Diseases; Climacteric; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lignans; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Tumor Cells, Cultured

Topics: Animals; Estrogens, Non-Steroidal; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Risk Factors

Topics: Animals; Antioxidants; Diet; Disease Models, Animal; Estrogens; Estrogens, Non-Steroidal; Female; Genistein; Growth Inhibitors; Heart Diseases; Humans; Isoflavones; Male; Neoplasms; Neoplasms, Experimental; Neovascularization, Pathologic; Phytoestrogens; Plant Preparations

Through an orderly sequence incorporating epidemiologic and laboratory research, human clinical/metabolic studies, and clinical intervention trials, the NCI develops and maintains cancer prevention and control programs that are directed toward the overall goal to reduce cancer incidence, morbidity, and mortality. Epidemiologic studies have shown correlations between consumption of numerous dietary constituents and cancer risk. Results of in vitro and animal studies have reinforced many of these epidemiologic associations and data from clinical/metabolic studies are being used to evaluate the relevance of these associations in humans. Although much remains to be learned about the influence of specific dietary constituents and dietary patterns on cancer risk, it is clear that diet can have a significant impact in cancer prevention and control. Investigations on the cellular and molecular effects of dietary constituents, as well as their metabolic and physiologic effects should provide better insight on the mechanisms of action of these dietary constituents. There also is a need to develop biomarkers of dietary intake that could be used to monitor compliance in intervention studies, as well as biomarkers as clinical trial endpoints that can be used to predict the emergence and progression of cancer. Working with other agencies and the private sector, the NCI will continue to design and implement information programs that translate the knowledge gained from these diet and cancer prevention studies to help Americans adopt dietary patterns that may reduce cancer risk. Continued emphasis will be placed on intervention programs targeted toward high-risk and underserved segments of the U.S. population in an effort to reduce the high incidence of cancers in these groups.

Topics: Animals; Antioxidants; Clinical Trials as Topic; Diet; Dietary Fats; Dietary Fiber; Estrogens, Non-Steroidal; Female; Folic Acid; Health Education; Humans; Isoflavones; Male; National Institutes of Health (U.S.); Neoplasms; Phytoestrogens; Plant Preparations; Research Design; Risk Factors; United States

Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.

Topics: Animals; Antineoplastic Agents; Diet; Estrogens; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Incidence; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Plant Preparations; Risk Factors

The wide distribution of plant estrogens or 'phytoestrogens' in cereals, vegetables and medicinal plants raises questions concerning the possible health risks and benefits associated with their consumption. In this article, we provide a synopsis of the literature relating principally to the clinical effects of phytoestrogens on the diseases associated with ageing. The sources, metabolism and properties of the different phytoestrogens are also discussed. The studies included were primarily restricted to those with data pertinent to clinical practice. Our contention is that phytoestrogens are at least part of the reason why vegetarians and Asian populations have a low rate of cancer and heart disease.

Topics: Adult; Aged; Climacteric; Colorectal Neoplasms; Coronary Disease; Cross-Cultural Comparison; Diet, Vegetarian; Estrogens, Non-Steroidal; Feeding Behavior; Female; Glycine max; Humans; Isoflavones; Male; Middle Aged; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

Lignans and phytoestrogens have been associated with protective effect against hormone-related diseases, for example, cancer of the breast and prostate, and potential mechanisms for this effect have been reported. Antioxidants also appear to have some protective effect against diseases associated with reactive free radicals such as coronary heart disease and cancer. Whole grains contain some of these substances particularly the mammalian lignan precursors, vitamin E, other phenolic compounds, Se, and phytic acid. These substances may in part be responsible for the reduced risk of cancer and coronary heart disease associated with intake of high-fiber diets containing whole grains. Because they are more associated with the fiber in the outer layers of the grain, the intake of whole vs. refined grain is emphasized for optimum health benefits.

Topics: Antioxidants; Edible Grain; Estrogens; Estrogens, Non-Steroidal; Health Promotion; Heart Diseases; Hormones; Humans; Isoflavones; Lignans; Neoplasms; Phytoestrogens; Plant Preparations

Oxidative damage to lipids may be involved in the etiology of atherosclerosis, cardiovascular disease in general, and cancer. The soy isoflavone phytoestrogens, genistein and daidzein, and equol (a daidzein metabolite produced by intestinal microflora) are antioxidants in vitro; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation.. We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation, compared with a diet enriched with soy from which the isoflavones had been extracted.. : A randomized, crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects. Plasma concentrations of an F(2)-isoprostane, 8-epi-prostaglandin F(2)(alpha) (8-epi-PGF(2)(alpha)), a biomarker of in vivo lipid peroxidation, and resistance of LDL to copper-ion-induced oxidation were determined.. Plasma concentrations of 8-epi-PGF(2)(alpha) were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment (326 +/- 32 and 405 +/- 50 ng/L, respectively; P = 0.028) and the lag time for copper-ion-induced LDL oxidation was longer (48 +/- 2.4 and 44 +/- 1.9 min, respectively; P = 0.017). Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde, LDL alpha-tocopherol, polyunsaturated fatty acids, and isoflavonoids did not differ significantly between dietary treatments.. Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation. This antioxidant action may be significant with regard to risk of atherosclerosis, cardiovascular disease in general, and cancer.

Topics: Adult; Cardiovascular Diseases; Cross-Over Studies; Diet; Dinoprost; Estrogens, Non-Steroidal; F2-Isoprostanes; Female; Glycine max; Humans; Isoflavones; Lipid Peroxidation; Lipoproteins, LDL; Male; Neoplasms; Phytoestrogens; Plant Preparations

Evidence regarding dietary phytoestrogens in relation to mortality remains limited.. The objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females.. We followed 75,981 females in the Nurses' Health Study (1984-2018) and 44,001 males in the Health Professionals Follow-up Study (1986-2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history.. During 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality.. A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

Topics: Adult; Cardiovascular Diseases; Cause of Death; Coumarins; Diet; Female; Follow-Up Studies; Humans; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Prospective Studies

Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women's health. Our previous work showed that P. dioica extracts were oestrogenic.. This work identifies phytochemicals from P. dioica that are responsible for the plant's oestrogen-like activities.. P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50 μg/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1 μM in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR.. Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Binding, Competitive; Cell Proliferation; Chromones; Dose-Response Relationship, Drug; Estrogen Receptor Modulators; Female; Humans; Inhibitory Concentration 50; MCF-7 Cells; Neoplasms; Phytoestrogens; Phytotherapy; Pimenta; Plant Extracts; Plant Leaves; Plants, Medicinal; Receptors, Estrogen

Dehydroeffusol (DHE) is a phenanthrene isolated from the Chinese medicinal plant Juncus effusus. Biological evaluation of DHE reveals in vitro and in vivo anticancer effects. We performed a shotgun proteomic analysis using liquid chromatography-tandem mass spectrometry to investigate the changes in the protein profiles in cancer cells upon DHE treatment. DHE affected cancer-associated signaling pathways, including NF-κB, β-catenin, and endoplasmic reticulum stress. Through quantitative pathway and key node analysis of the proteomics data, activating transcription factor 2 (ATF-2) and c-Jun kinase (JNK) were found to be the key components in DHE's modulated biological pathways. Based on the pathway analysis as well as chemical similarity to estradiol, DHE is proposed to be a phytoestrogen. The proteomic, bioinformatic, and chemoinformatic analyses were further verified with individual cell-based experiments. Our study demonstrates a workflow for identifying the mechanisms of action of DHE through shotgun proteomic analysis.

Topics: Activating Transcription Factor 2; Antineoplastic Agents; JNK Mitogen-Activated Protein Kinases; Neoplasms; Phenanthrenes; Phytochemicals; Phytoestrogens; Poaceae; Proteomics; Signal Transduction

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cross-Sectional Studies; Diet, Healthy; Female; Heart Diseases; Humans; Mexico; Middle Aged; Neoplasms; Nutrition Surveys; Obesity; Overweight; Patient Compliance; Phytoestrogens; Prevalence; Risk

Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR. Treatment with genistein induced cell death in a concentration-dependent manner in cancer cells from diverse tissue origins, but not in non-transformed cells such as hTERT-RPE or MCF10A cells. We also observed that genistein tended to be more selective against cancer cells with mutations in the TP53 gene. TP53-depeleted LNCaP and NCI-H460 cells using shRNA targeting human TP53 were more sensitive to cell death by treatment of genistein. Furthermore, genistein induced mitotic arrest by inhibiting Plk1 activity and, consequently, led to mitotic catastrophe and apoptosis. These data suggest that genistein may be a promising anticancer drug candidate due to its inhibitory activity against Plk1 as well as EGFR and effectiveness toward cancer cells, especially those with p53-mutation. J. Cell. Physiol. 232: 2818-2828, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Antineoplastic Agents, Hormonal; Apoptosis; Cell Cycle Proteins; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; ErbB Receptors; G2 Phase Cell Cycle Checkpoints; Genistein; HCT116 Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Mutation; Neoplasms; Phytoestrogens; Polo-Like Kinase 1; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; RNA Interference; Signal Transduction; Transfection; Tumor Suppressor Protein p53

Experimental studies suggest that phytoestrogen intake alters cancer and cardiovascular risk. This study investigated the associations of urinary phytoestrogens with total cancer (n = 79), cardiovascular (n = 108), and all-cause (n = 290) mortality among 5179 participants in the continuous National Health and Nutrition Examination Survey (1999-2004).. Urinary phytoestrogens were measured using high-performance liquid chromatography with tandem mass spectrometric detection. Survival analysis was performed to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for each of the three outcomes in relation to urinary phytoestrogens.. After adjustment for confounders, higher urinary concentrations of total enterolignans were associated with a reduced risk of death from cardiovascular disease (HR for tertile 3 vs. tertile 1 0.48; 95 % CI 0.24, 0.97), whereas higher urinary concentrations of total isoflavones (HR for tertile 3 vs. tertile 1 2.14; 95 % CI 1.03, 4.47) and daidzein (HR for tertile 3 vs. tertile 1 2.05; 95 % CI 1.02, 4.11) were associated with an increased risk. A reduction in all-cause mortality was observed for elevated urinary concentrations of total enterolignans (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.43, 0.96) and enterolactone (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.44, 0.97).. Some urinary phytoestrogens were associated with cardiovascular and all-cause mortality in a representative sample of the US population. This is one of the first studies that used urinary phytoestrogens as biomarkers of their dietary intake to evaluate the effect of these bioactive compounds on the risk of death from cancer and cardiovascular disease.

Topics: 4-Butyrolactone; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Isoflavones; Lignans; Male; Middle Aged; Mortality; Neoplasms; Nutrition Surveys; Phytoestrogens; Proportional Hazards Models; Risk Factors; Treatment Outcome

The effects of miroestrol (MR), an active phytoestrogen from Pueraria candollei var. mirifica, on expression of cancer-related genes were determined.. Seven-week-old female ICR mice (n = 5 each) were subcutaneously administered estradiol (E2, 0.5 mg/kg/day) or MR (0.5 or 5 mg/kg/day) daily for 7 days. Some were given ER or MR in combination with β-naphthoflavone (BNF, 30 mg/kg/day) for the last 3 days. The expression of cancer-related genes including cytochrome P450 1A (Cyp1a), cytochrome P450 1B1 (Cyp1b1), aromatase P450 (Cyp19), NAD(P)H: quinone oxidoreductase 1 (Nqo1) and catechol-O-methyltransferase (Comt) were evaluated.. In the presence of BNF, MR suppressed hepatic CYP1A1 activity and CYP1A2 activity, expression of CYP1B1 mRNA and expression of CYP1A1/2 and CYP1B1 protein. E2, by contrast, did not. MR restored expression levels of hepatic NQO1 and uterine COMT in BNF-treated mice. Furthermore, MR increased expression of uterine CYP19 to the same extent as E2.. MR may be superior to E2 as it downregulates expression of CYP1. Moreover, MR normalized expression of both NQO1 and COMT, the protective enzymes, in murine liver and uteri. These results support the use of MR as an alternative supplement for menopausal women, MR having the extra benefit of reducing cancer risk.

Topics: Animals; beta-Naphthoflavone; Catechol O-Methyltransferase; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Cytochrome P450 Family 19; Estradiol; Estrogen Replacement Therapy; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Liver; Mice, Inbred ICR; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Phytoestrogens; Steroids; Uterus

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%).

Topics: Adult; Aged; Bread; Butylene Glycols; Cardiovascular Diseases; Diet; Feeding Behavior; Female; Flax; Furans; Humans; Latvia; Lignans; Male; Middle Aged; Neoplasms; Phenols; Phytoestrogens; Plant Extracts; Sex Factors

Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.. Single 24-hour dietary recalls were collected from 36,037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres.. Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages.. There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

Topics: Adult; Aged; Beverages; Body Mass Index; Cardiovascular Diseases; Coumarins; Diet; Edible Grain; Energy Intake; Equol; Europe; Female; Fruit; Glycine max; Humans; Isoflavones; Life Style; Lignans; Male; Middle Aged; Neoplasms; Nutritional Status; Phytoestrogens; Prospective Studies; Vegetables

Topics: Diet; Energy Intake; Female; Humans; Male; Neoplasms; Nutritional Status; Phytoestrogens

Topics: Diet; Energy Intake; Female; Humans; Male; Neoplasms; Nutritional Status; Phytoestrogens

The health benefits associated with soya food consumption have been widely studied, with soya isoflavones and soya protein implicated in the protection of CVD, osteoporosis and cancers such as those of the breast and prostate. Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman), a metabolite of the soya isoflavone daidzein, is produced via the formation of the intermediate dihydrodaidzein, by human intestinal bacteria, with only approximately 30-40% of the adult population having the ability to perform this transformation following a soya challenge. Inter-individual variation in conversion of daidzein to equol has been attributed, in part, to differences in the diet and in gut microflora composition, although the specific bacteria responsible for the colonic biotransformation of daidzein to equol are yet to be identified. Equol is a unique compound in that it can exert oestrogenic effects, but is also a potent antagonist of dihydrotestosterone in vivo. Furthermore, in vitro studies suggest that equol is more biologically active than its parent compound, daidzein, with a higher affinity for the oestrogen receptor and a more potent antioxidant activity. Although some observational and intervention studies suggest that the ability to produce equol is associated with reduced risk of breast and prostate cancer, CVD, improved bone health and reduced incidence of hot flushes, others have reported null or adverse effects. Studies to date have been limited and well-designed studies that are sufficiently powered to investigate the relationship between equol production and disease risk are warranted before the clinical relevance of the equol phenotype can be fully elucidated.

Topics: Antioxidants; Bone Diseases; Cardiovascular Diseases; Dihydrotestosterone; Equol; Glycine max; Hot Flashes; Humans; Intestinal Mucosa; Intestines; Isoflavones; Neoplasms; Phenotype; Phytoestrogens; Phytotherapy; Plant Extracts; Receptors, Estrogen; Risk Factors

Advancements in management protocols and chemotherapeutics have improved outcomes for patients diagnosed with cancer. Cancer, however, continues to claim many lives annually in the United States and around the world. There is a large body of evidence that is strong and consistent that through modification of diet and lifestyle habits, cancer can be a preventable disease. This article discusses these changes and highlights the evidence for and against implementing them.

Topics: Alcoholic Beverages; Breast Feeding; Diet; Dietary Supplements; Exercise; Health Behavior; Humans; Mass Screening; Neoplasms; Obesity; Phytoestrogens; Primary Health Care; Primary Prevention; Risk Factors; Smoking; Sunscreening Agents

Topics: Antioxidants; Diet; Humans; Menopause; Neoplasms; Pancreatic Neoplasms; Phytoestrogens

Epidemiological studies suggest that individuals with elevated plasma concentrations of insulin-like growth factor (IGF-I) are at increased risk of developing cancer. We assessed whether dietary intake of total energy, protein, alcohol, phytoestrogens and related foods, and tomatoes and lycopene was associated with plasma levels of IGF-I and IGF binding proteins (IGFBPs) in Dutch women.. A cross-sectional study was conducted in 224 premenopausal and 162 postmenopausal women, aged 49-69, participating in the Prospect-EPIC study in the Netherlands. Diet was assessed using a food frequency questionnaire.. In postmenopausal women, higher alcohol intake was associated with lower plasma IGFBP-1 concentrations (alcohol 1.4 to 20 g/day: 20% decrease in IGFBP-1; p = 0.04), and higher intake of plant lignans was associated with higher IGFBP-1 concentrations (plant lignans 0 to 1 mg/day: 59% increase in IGFBP-1; p =0.02). Higher soy intake was associated with higher plasma IGFBP-2 concentrations in premenopausal women (soy 0 to 2.5 g/day: 3% increase in IGFBP-2; p = 0.04). No independent associations of dietary factors with IGF-I or IGFBP-3 concentrations were observed. However, in premenopausal women alcohol intake was inversely associated with IGF-I and positively associated with IGFBP-3 after mutual adjustment.. In this study population, with limited variation in dietary intake, total energy, protein, phytoestrogens and lycopene were not associated with IGF-I and IGFBP-3. Alcohol was inversely, and some measures of phytoestrogen intake were positively associated with plasma IGFBP-1 or -2 concentrations. The roles of IGFBP-1 and -2 in relation to IGF-I bioactivity and cancer deserve further investigation.

Topics: Aged; Cross-Sectional Studies; Diet; Energy Intake; Epidemiologic Studies; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Middle Aged; Neoplasms; Netherlands; Phytoestrogens; Postmenopause; Pregnancy Proteins; Premenopause; Risk Factors; Vegetables

Topics: Complementary Therapies; Estrogens, Non-Steroidal; Humans; Isoflavones; Naturopathy; Neoplasms; Phytoestrogens; Plant Preparations; Quality Control

Topics: Calibration; Cohort Studies; Estrogens, Non-Steroidal; Europe; Female; Glycine max; Humans; Isoflavones; Male; Mental Recall; Neoplasms; Phytoestrogens; Plant Preparations; Prospective Studies; Seasons; Soybean Proteins

Topics: Calibration; Cohort Studies; Dairy Products; Diet, Vegetarian; Estrogens, Non-Steroidal; Europe; Female; Food, Organic; Glycine max; Humans; Isoflavones; Male; Mental Recall; Middle Aged; Neoplasms; Phytoestrogens; Plant Preparations; Prospective Studies; Seasons; Soybean Proteins

Topics: Adrenergic alpha-Agonists; Antineoplastic Agents; Estrogens; Estrogens, Non-Steroidal; Female; Glycine max; Hot Flashes; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Selective Serotonin Reuptake Inhibitors

An integrated QSAR model has been formulated to predict estrogenic, carcinogenic, and cancer protective effects of phytoestrogens (PE). Relative binding of PEs to estrogen receptors ER alpha and ER beta exhibited a parabolic relationship with dipole moment (mu). The high-affinity binding of PEs to ER alpha correlated with Dif0 (0 chi-0 chi v difference index encoding nonsigma electronic charge), while the low-affinity binding of PEs to ER alpha correlated with H bonding (positive coefficient) and % hydrophilic surface (negative coefficient). The high-affinity binding of PEs to ER beta correlated with molecular with (MWd) and Dif0, while the low-affinity binding of PEs to ER beta correlated with H bonding (positive coefficient) and hydrophilic-lipophilic balance (negative coefficient). Thus an increase in electronic or ionic charge, formation of H bonds, or a decrease in hydrophilic property of PEs may increase their binding to ER. The relative transcription activity (RTA) of ER alpha correlated with Dif0-Dif1, while RTA of ER beta correlated with H bonding and polarity. The PE-induced stimulation of DNA synthesis in estrogen-sensitive breast cancer (BC) cells correlated positively with (MD*4 chi v) where MD is molecular depth and 4 chi v is the valence of a 4th order fragment. IC50 for PE-induced inhibition of DNA synthesis in estrogen-sensitive BC cells correlated with (MD*Log P) and Dif3 (3 chi-3 chi v difference index encoding nonsigma electronic charge of fragments consisting of four atoms and three bonds) and Dif3(2). IC50 for PE-induced inhibition of DNA synthesis in estrogen-independent cancer cell lines correlated with (MD*Log P) and 1/water solubility. Thus molecular shape and molecular connectivity of PEs play a key role in modulating estrogen-induced transactivation activity and DNA synthesis in BC cells.

Topics: Amino Acid Sequence; Animals; Anticarcinogenic Agents; Breast Neoplasms; Carcinogens; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Molecular Sequence Data; Neoplasms; Phytoestrogens; Plant Preparations; Quantitative Structure-Activity Relationship; Rats; Receptors, Estrogen; Sequence Alignment; Sequence Homology, Amino Acid

Topics: Diet; Estrogens, Non-Steroidal; Feeding Behavior; Food; Food Analysis; Food Preferences; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible; Surveys and Questionnaires

Phytoestrogens (weak estrogens found in plants or derived from plant precursors by human metabolism) have been hypothesized to reduce the risk of a number of cancers. However, epidemiologic studies addressing this issue are hampered by the lack of a comprehensive phytoestrogen database for quantifying exposure. The purpose of this research was to develop such a database for use with food-frequency questionnaires in large epidemiologic studies.. The database is based on consumption patterns derived from semistructured interviews with 118 African-American, Latina, and white women residing in California's San Francisco Bay Area. HPLC-mass spectrometry was used to determine the content of seven specific phytoestrogenic compounds (i.e. the isoflavones: genistein, daidzein, biochanin A, and formononetin; the coumestan: coumestrol; and the plant lignans: matairesinol and secoisolariciresinol) in each of 112 food items/groups.. Traditional soy-based foods were found to contain high levels of genistein and daidzein, as expected, as well as substantial amounts of coumestrol. A wide variety of "hidden" sources of soy (that is, soy protein isolate, soy concentrate, or soy flour added to foods) was observed. Several other foods (such as various types of sprouts and dried fruits, garbanzo beans, asparagus, garlic, and licorice) were also found to be substantial contributors of one or more of the phytoestrogens analyzed.. Databases, such as the one described here, are important in assessing the relationship between phytoestrogen exposure and cancer risk in epidemiologic studies. Agencies, such as the United States Department of Agriculture (USDA), that routinely provide data on food composition, on which epidemiologic investigations into dietary health effects are based, should consider instituting programs for the analysis of phytochemicals, including the phytoestrogens.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Databases, Factual; Epidemiologic Studies; Estrogens, Non-Steroidal; Female; Food; Food Analysis; Food Preferences; Humans; Isoflavones; Mass Spectrometry; Middle Aged; Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible; Surveys and Questionnaires; United States

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food-frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.

Topics: Anticarcinogenic Agents; Databases, Factual; Diet Records; Estrogens, Non-Steroidal; Humans; Isoflavones; Neoplasms; Nutrition Assessment; Phytoestrogens; Plant Preparations; Software Design; Surveys and Questionnaires

Topics: Animals; Bone Density; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Neoplasms; Phytoestrogens; Plant Preparations; Soybean Proteins

Topics: Animals; Cardiovascular Diseases; Estrogens, Non-Steroidal; Humans; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations

Topics: Animals; Estrogens; Estrogens, Non-Steroidal; Flavonoids; Glycine max; Humans; Isoflavones; Neoplasms; Neoplasms, Experimental; Phytoestrogens; Plant Preparations; Tea

Topics: Animals; Carbazoles; Estrogen Antagonists; Estrogens; Estrogens, Non-Steroidal; Humans; Indoles; Isoflavones; Neoplasms; Neoplasms, Experimental; Phytoestrogens; Plant Preparations; Plants