glycitein and Breast-Neoplasms

The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.

Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Carcinogens; China; Clinical Trials as Topic; Congresses as Topic; Disease Models, Animal; Female; Genistein; Humans; Isoflavones; Los Angeles; Neoplasms, Hormone-Dependent; Phytoestrogens; Population Surveillance; Receptors, Estrogen; Risk Factors; Soy Foods

Topics: Anticarcinogenic Agents; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Glycine max; Humans; Isoflavones; MCF-7 Cells

Glycitein is an O-methylated isoflavone which accounts for 5-10% of the total isoflavones in soy food products. Cell proliferation studies on the dietary phytoestrogen, glycitein against human breast carcinoma SKBR-3 cells showed that glycitein exhibits biphasic regulation on SKBR-3 cells. At concentrations of less than 10 mg/mL, cells respond to glycitein by increasing cell growth and de novo DNA synthesis whereas the addition of glycitein at concentrations greater than 30 mg/mL significantly inhibited cell growth and DNA synthesis in a dose-dependent manner. Cells treated with 60 mg/mL of glycitein did not regain normal growth after treatment was stopped. Glycitein was found to be cytostatic at low concentrations and cytotoxic at higher concentrations. Treatment with 100 mg/mL of glycitein severely altered the cell morphology. Collective results showed that glycitein damaged the cell membranes by increasing membrane permeability and suggested possible mechanisms of the action of dietary phytoestrogens on human breast carcinoma SKBR-3 cells.

Topics: Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Genistein; Humans; Isoflavones; Phytoestrogens

To assess dietary isoflavone intake between population and hospital outpatient controls and examine if cancer risks estimated for isoflavone using hospital outpatient controls would be different from those using population controls. Three parallel case-control studies on leukemia, breast, and colorectal cancers in China in 2009-2010 were conducted, using population and hospital outpatient controls to separately match 560 incident cases at a 1:1 ratio. A validated food frequency questionnaire was administered by face-to-face interview. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The 2 control groups had closely similar distributions of dietary isoflavone intake. Risk estimates for breast cancers were adjusted ORs (95% CI) of 0.39 (0.23-0.66) and 0.31 (0.18-0.55) for daidzein, 0.35 (0.20-0.61) and 0.28 (0.16-0.52) for genistein, 0.66 (0.41-1.08) and 0.53 (0.32-0.88) for glycitein, and 0.53 (0.33-0.85) and 0.43 (0.26-0.71) for total isoflavone using hospital outpatient and population controls respectively. The study found that hospital outpatient controls were comparable to population controls in measured dietary intake of isoflavone in the Chinese hospital setting.

Topics: Adult; Aged; Breast Neoplasms; Case-Control Studies; China; Colorectal Neoplasms; Diet; Female; Genistein; Humans; Isoflavones; Leukemia; Male; Middle Aged; Neoplasms; Odds Ratio; Outpatient Clinics, Hospital; Risk Factors

Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappaB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17beta-estradiol (E(2)). E(2) increased cell growth significantly, coumestrol increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G(1)/S transition in cell cycle analysis, similar to E(2). This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein. Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-kappaB-dependent transcriptional activity. On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) alpha silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERalpha silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity.

Topics: Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Coumestrol; Estradiol; Estrogen Receptor alpha; Female; Genistein; Humans; Isoflavones; Phytoestrogens; Proto-Oncogene Proteins c-bcl-2; Resveratrol; Stilbenes

Isoflavonoids are a group of biologically active phytochemicals that humans are exposed to mainly through soy food intake. Because of the similar chemical structure of these compounds and estradiol, it has been hypothesized that isoflavonoids may be related to the risk of breast cancer. Overnight urine samples from 60 incident breast cancer cases and their individually matched controls were assayed for urinary excretion rates of five major isoflavonoids (daidzein, genistein, glycitein, equol, and O-desmethylangolensin) and total phenols. These subjects were from a large population-based case-control study conducted in Shanghai, and urine samples from breast cancer cases were collected before any cancer therapy to minimize the potential influence of the disease and its sequelae on study results. Urinary excretion of total phenols and all individual isoflavonoids, particularly glycitein, was substantially lower in breast cancer cases than controls. For total isoflavonoids, the mean excretion was 13.95 nmol/mg creatinine (SD, 20.76 nmol/mg creatinine) for cases and 19.52 nmol/mg creatinine (SD, 25.36 nmol/mg creatinine) for controls (P for difference = 0.04). The case-control difference was more evident when median levels of these compounds were compared, with the median excretion of all major isoflavonoids being 50-65% lower in cases than in controls. Individuals in the highest tertile of daidzein, glycitein, and total isoflavonoids had about half the cancer risk of those in the lowest tertile. The adjusted odds ratio for breast cancer was 0.14 (95% confidence interval, 0.02-0.88) for women whose urinary excretion of both phenol and total isoflavonoids was in the upper 50% compared with those in the lower 50%. The results from this study support the hypothesis that a high intake of soy foods may reduce the risk of breast cancer.

Topics: Adult; Anticarcinogenic Agents; Breast Neoplasms; Case-Control Studies; China; Chromans; Confidence Intervals; Creatinine; Equol; Estradiol; Estrogens, Non-Steroidal; Feeding Behavior; Female; Genistein; Glycine max; Humans; Isoflavones; Middle Aged; Monoamine Oxidase Inhibitors; Odds Ratio; Phenols; Risk Factors