Widespread epidemiological data support the notion that high isoflavoves intake is safe and provides health benefits similar to estrogen. Isoflavones have been reported to regulate genes that are involved in several cellular events, such as control of cell proliferation, cell cycle, cell apoptosis, transcription regulation, cancer invasion and metastasis and so on. Previously, soy isoflavones have been demonstrated to have a tumor suppressor effect on bladder cancer. We earlier identified 71 candidate bladder tumor suppressors by using the isoflavones treatment vs. non-treatment in RT4 (Stage I, TMN) cells in conjunction with the strategy of suppression subtractive cDNA libraries. In a preliminary screening, epithelial membrane protein 2 (EMP2) mRNA was downregulated in higher TMN-grade bladder tumor cells. In this study, we aim at the mechanism of isoflavones upregulation of the candidate bladder tumor suppressor: EMP2. In order to clarify the regulatory mechanism, we have constructed a series of 5¡¦ deletion fragment of EMP2 promoter (-1,420 to +268 bp) into a luciferase reporter plasmid pGL3-baisc and analyzed the promoter activity. The rapidly loss of the promoter activities when the region between pH (-44 to +268) and pI (-24 to +268) is deleted, suggesting that at least one critical transcriptional factor binding site may exist between -44 to -24 bp region. By bioinformatics, the transcription factor CREB1 binding site is predicted in the critical region. The ChIP assay and site-directed mutagenesis of the CREB site reveal its critical role for the EMP2 transcription. The EMP2 mRNA is downregulated after knock-down of CREB1 protein by shCREB1 in J82 cells. It can be evidence for EMP2 transcription is regulated by transcription factor CREB1. In investigations of genistein (one component of isoflavones) up-regulated EMP2 transcripts, we find there are consistent results for genistein upregulated of EMP2 promoter region. In conclusion, transcription factor CREB1 plays an important role in the regulation of EMP2 transcription.

Many studies show that estradiol (E2) and consumption of soy and its primary phytoestrogen component genistein (GEN) can inhibit the formation of colon tumors. However, the effects of E2 and GEN at physiologically relevant levels in non-diseased colonocytes have yet to be investigated. We hypothesized that E2 and GEN could prove to be chemo-protective agents in the colon by moderately increasing apoptosis and decreasing proliferation in a healthy system. Thus, the presented studies focused on evaluating the effects of E2 and GEN in non-malignant colonocytes in vitro and in vivo to determine how the compounds influence the physiology of these cells. E2 (1 nM/L) and GEN treatments (1 and 10 microM/L) decreased cell growth, increased apoptosis, and increased p53 transcriptional activity in young adult mouse colonocytes, a non-malignant cell line. To study further the effects of E2 and GEN in healthy colonic epithelia, we evaluated physiologic changes in colonic crypts in ovariectomized mice given an E2 pellet, 1,000 ppm GEN diet, or a phytoestrogen free diet. As seen in vitro, E2 treated animals had significantly higher rates of apoptosis with GEN trending in the same fashion. These data demonstrate that E2 and GEN alter the physiology of non-malignant colonocytes. Collectively, with our previous data, this suggests that E2 and GEN influence colonocyte physiology and this state may partially explain how these compounds decrease risk of colon cancer.

The objective of this study was to evaluate the effects of orally administered soy-derived extracts on normal reproductive development in neonatal pigs as a model for infants on soy formula. Yorkshire-Landrace crossbred sows were randomly assigned to a lactating diet supplemented with either Novasoy 70 or without. Feed was top-dressed from d 100 of gestation until farrowing. Neonatal pigs (NPs) were weighed on post natal day (PND) six then randomly assigned to one of four treatments 1) control, 2) estradiol, 3) low, or 4) high genistein dose. This study demonstrates that oral exposure of NPs to estradiol but not genistein alters reproductive tract development and that this effect may be amplified from in utero exposure to sow diets with elevated concentrations of phytoestrogens. Thus, the neonatal pig may provide a useful model for assessing effects of dietary phytoestrogens on reproductive development in infants on soy-based formulas.

No description available.

Thesis (M.S.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references (ℓ. 107-127)

abstract: Introduction: Cystic fibrosis (CF) is the most common life-shortening autosomal recessive genetic disease affecting Caucasians. The disease is characterized by a dysfunctional cystic fibrosis transmembrane regulator (CFTR) protein and aberrant mucus accumulation that subsequently alters the physicochemical environment in numerous organ systems. These mucosal perturbations have been associated with inflammation and microbial dysbiosis, most notably in the lungs and gastrointestinal (GI) tract. Genistein, a soy isoflavone and dietary polyphenol, has been shown to modulate CFTR function in cell cultures and murine models, as well exert sex-dependent improvement of survival rates in a CF mouse model. However, it is unknown whether dietary genistein affects gut microbiome diversity and community structure in cystic fibrosis. This study sought to examine associations between dietary genistein treatment and gut microbiome diversity and community structure in a murine model of CF. Methods: Twenty-four male and female mice homozygous for the DF508 CFTR gene mutation were maintained on one of three diet regimens for a 45-day period (n=11, standard chow; n=7, Colyte-treated water and standard chow; n=6, 600 mg dietary genistein per kg body weight). One fecal pellet was collected per mouse post-treatment, and microbial genomic DNA was extracted from the fecal samples, quantified, amplified, and sequenced on the Illumina MiSeq platform. QIIME 2 was used to conduct alpha- and beta-diversity analyses on all samples. Results: Measures of alpha-diversity were significantly decreased in the dietary genistein group as compared to either standard chow or Colyte groups. Measures of beta-diversity showed that community structure differed significantly between dietary treatment groups; these differences were further illustrated by distinct clustering of taxa as shown by principal coordinates analysis plots. Conclusion: This 3-arm parallel experimental study showed that dietary genistein treatment was associated with decreased microbial diversity and differences in microbial community structure in DF508 mice. / Dissertation/Thesis / Masters Thesis Nutrition 2019

The effects of the fenretinide and genistein as single or combined drugs on ovarian cancer proliferation and viability were investigated. Hypothesis: Co-treatment with genistein will enable a lower dose of fenretinide to be effective in inhibiting the proliferation and survival of ovarian cancer cells. Methods: Low and high doses of genistein and fenretinide were tested on A2780s and A2780cp cells using trypan blue viable cell count, MTS assay. Results and conclusions: Unlike low doses of fenretinide, genistein had anti-proliferative effects on both cell lines. There were no additive or synergistic effects of the two compounds. Higher dose treatments induced anti-proliferative effects and apoptotic cell death in both A2780s and A2780cp cells, with a greater sensitivity of A2780s cells to both test compounds. Overall Conclusion: Genistein and higher doses of fenretinide similarly impair cell cycle progression and induce apoptosis. The anti-proliferative effects of genistein can be affected by co-treatment with fenretinide

Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.

Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.

The effects of the fenretinide and genistein as single or combined drugs on ovarian cancer proliferation and viability were investigated. Hypothesis: Co-treatment with genistein will enable a lower dose of fenretinide to be effective in inhibiting the proliferation and survival of ovarian cancer cells. Methods: Low and high doses of genistein and fenretinide were tested on A2780s and A2780cp cells using trypan blue viable cell count, MTS assay. Results and conclusions: Unlike low doses of fenretinide, genistein had anti-proliferative effects on both cell lines. There were no additive or synergistic effects of the two compounds. Higher dose treatments induced anti-proliferative effects and apoptotic cell death in both A2780s and A2780cp cells, with a greater sensitivity of A2780s cells to both test compounds. Overall Conclusion: Genistein and higher doses of fenretinide similarly impair cell cycle progression and induce apoptosis. The anti-proliferative effects of genistein can be affected by co-treatment with fenretinide