-
World Journal of Gastroenterology Mar 2004To study the effects of daidzein on human pancreatic cancer cells in vitro.
AIM
To study the effects of daidzein on human pancreatic cancer cells in vitro.
METHODS
Human estrogen-receptor (ER)-positive pancreatic cancer cells MiaPaCa-2 and ER-negative pancreatic cancer cells PANC-1 were treated by 0.1 micromol/L, 1 micromol/L, 10 microL, 25 microL, 50 microL, 75 microL and 100 microL of daidzein, respectively. Its antiproliferative effect was studied by MTT assay.
RESULTS
Daidzein inhibited the growth of MiaPaCa-2 and PANC-1 cells at the concentrations from 0.1 microL to 100 microL. A dose- and time-dependent manner was found. The IC(50) of daidzein on MiaPaCa-2 and PANC-1 cells was 45 microL and 75 micro, respectively. After MiaPaCa-2 cells were treated by daidzein for 3 d and at the concentrations more than IC(50), the inhibitory manner was identical and the inhibition appeared a saturation phenomenon, but the inhibitory manner of daidzein on PANC-1 cells was different from that of MiaPaCa-2 cells.
CONCLUSION
Daidzein has antiproliferative effects on human estrogen-receptor-positive and negative pancreatic cancer cells, but their mechanisms may be different.
Topics: Cell Line, Tumor; Estrogens, Non-Steroidal; Humans; Isoflavones; Pancreatic Neoplasms; Receptors, Estrogen
PubMed: 15040033
DOI: 10.3748/wjg.v10.i6.860 -
The International Journal of Biological... 2002Daidzein and its main metabolite equol are isoflavone phytoestrogens. Several studies have suggested that intake of an isoflavone-rich diet may prevent hormone-related...
Daidzein and its main metabolite equol are isoflavone phytoestrogens. Several studies have suggested that intake of an isoflavone-rich diet may prevent hormone-related cancer and estrogen-related disorders (cardiovascular disease, osteoporosis and menopausal symptoms). To better understand the role of isoflavones in preventing such severe disease, several methods have been developed to measure these compounds in biological fluids. However, the analytical procedures to measure isoflavones are often time-consuming and require highly skilled technicians. In this paper we describe a method for urinary daidzein and equol measurement that combines solid phase extraction and HPLC purification before gas chromatographic determination. The specificity of the method was confirmed by the gas chromatography-mass spectrometry technique. The mean recovery of daidzein and equol was 94.6% and 97.0%, respectively. The repeatability of the method was in the range of 2.0-7.4% for daidzein and 1.3-4.9% for equol. A linear relationship between observed and expected values was found in the dilution (r2=0.9983 for daidzein; r2=0.9982 for equol) and addition (r2=0.9984 for daidzein; r2=0.9989 for equol) assays. The method is suitable to measure changes in the urinary excretion of isoflavones and to investigate urinary isoflavonoids as biomarkers of isoflavone exposure.
Topics: Chromans; Chromatography, Gas; Chromatography, High Pressure Liquid; Equol; Female; Humans; Isoflavones; Middle Aged; Postmenopause
PubMed: 12408469
DOI: 10.1177/172460080201700307 -
Nutrients Nov 2012Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for... (Review)
Review
Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.
Topics: Absorption; Bone Density; Calcium; Drug Synergism; Female; Genistein; Hip Fractures; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Postmenopause; Risk Factors; Glycine max; Vitamin D
PubMed: 23201836
DOI: 10.3390/nu4111610 -
Oxidative Medicine and Cellular... 2019Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the / gene. The expanded CAG repeats...
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the / gene. The expanded CAG repeats encode a polyglutamine (polyQ) tract at the C-terminus of the ATXN3 protein. ATXN3 containing expanded polyQ forms aggregates, leading to subsequent cellular dysfunctions including an impaired ubiquitin-proteasome system (UPS). To investigate the pathogenesis of SCA3 and develop potential therapeutic strategies, we established induced pluripotent stem cell (iPSC) lines from SCA3 patients (SCA3-iPSC). Neurons derived from SCA3-iPSCs formed aggregates that are positive to the polyQ marker 1C2. Treatment with the proteasome inhibitor, MG132, on SCA3-iPSC-derived neurons downregulated proteasome activity, increased production of radical oxygen species (ROS), and upregulated the cleaved caspase 3 level and caspase 3 activity. This increased susceptibility to the proteasome inhibitor can be rescued by a Chinese herbal medicine (CHM) extract NH037 (from ) and its constituent daidzein via upregulating proteasome activity and reducing protein ubiquitination, oxidative stress, cleaved caspase 3 level, and caspase 3 activity. Our results successfully recapitulate the key phenotypes of the neurons derived from SCA3 patients, as well as indicate the potential of NH037 and daidzein in the treatment for SCA3 patients.
Topics: Adult; Aged; Animals; Caspase 3; Cell Death; Cell Differentiation; Female; Humans; Induced Pluripotent Stem Cells; Isoflavones; Leupeptins; Machado-Joseph Disease; Male; Mice; Middle Aged; Neurons; Oxidative Stress; Peptides; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein Aggregates; Pueraria; Ubiquitin
PubMed: 31687087
DOI: 10.1155/2019/8130481 -
Molecular Nutrition & Food Research Mar 2020To predict gut microbial metabolism of xenobiotics and the resulting plasma concentrations of metabolites formed, an in vitro-in silico-based testing strategy is...
SCOPE
To predict gut microbial metabolism of xenobiotics and the resulting plasma concentrations of metabolites formed, an in vitro-in silico-based testing strategy is developed using the isoflavone daidzein and its gut microbial metabolite S-equol as model compounds.
METHODS AND RESULTS
Anaerobic rat fecal incubations are optimized and performed to derive the apparent maximum velocities (V ) and Michaelis-Menten constants (K ) for gut microbial conversion of daidzein to dihydrodaidzein, S-equol, and O-desmethylangolensin, which are input as parameters for a physiologically based kinetic (PBK) model. The inclusion of gut microbiota in the PBK model allows prediction of S-equol concentrations and slightly reduced predicted maximal daidzein concentrations from 2.19 to 2.16 µm. The resulting predicted concentrations of daidzein and S-equol are comparable to in vivo concentrations reported.
CONCLUSION
The optimized in vitro approach to quantify kinetics for gut microbial conversions, and the newly developed PBK model for rats that includes gut microbial metabolism, provide a unique tool to predict the in vivo consequences of daidzein microbial metabolism for systemic exposure of the host to daidzein and its metabolite S-equol. The predictions reveal a dominant role for daidzein in ERα-mediated estrogenicity despite the higher estrogenic potency of its microbial metabolite S-equol.
Topics: Animals; Equol; Estrogen Receptor alpha; Feces; Female; Gastrointestinal Microbiome; Humans; Isoflavones; Liver; Male; Models, Theoretical; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 32027771
DOI: 10.1002/mnfr.201900912 -
Environmental Science & Technology Oct 2014The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a...
The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.
Topics: Agriculture; Androgens; Androstenedione; Animals; Diet; Environmental Monitoring; Equol; Estrogens; Estrone; Feces; Genistein; Hormones; Isoflavones; Phytoestrogens; Progesterone; Steroids; Swine; Urine
PubMed: 25148584
DOI: 10.1021/es5025806 -
The American Journal of Clinical... Apr 2010Despite decades of research on the relation between soy and breast cancer, questions regarding the absorption, metabolism, and distribution of isoflavones in breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Despite decades of research on the relation between soy and breast cancer, questions regarding the absorption, metabolism, and distribution of isoflavones in breast tissue largely remain unanswered.
OBJECTIVE
We evaluated the potential health effects of isoflavone consumption on normal breast tissue; isoflavone concentrations, metabolites, and biodistribution were investigated and compared with 17beta-estradiol exposure.
DESIGN
In this dietary intervention study, healthy women were randomly allocated to a soy milk (n = 11; 16.98-mg genistein and 5.40-mg daidzein aglycone equivalents per dose), soy supplement (n = 10; 5.27-mg genistein and 17.56-mg daidzein aglycone equivalents per dose), or control (n = 10) group. After a run-in period > or = 4 d, 3 doses of soy milk or soy supplements were taken daily for 5 d before an esthetic breast reduction. Blood and breast biopsies were collected during surgery and analyzed with liquid chromatography-tandem mass spectrometry.
RESULTS
After soy administration, genistein and total daidzein concentrations, which were expressed as aglycone equivalents, ranged from 135.1 to 2831 nmol/L and 105.1 to 1397 nmol/L, respectively, in hydrolyzed serum and from 92.33 to 493.8 pmol/g and 22.15 to 770.8 pmol/g, respectively, in hydrolyzed breast tissue. The major metabolites identified in nonhydrolyzed samples were genistein-7-O-glucuronide and daidzein-7-O-glucuronide, with an overall glucuronidation of 98%. Total isoflavones showed a breast adipose/glandular tissue distribution of 40:60, and their mean (+/-SEM) derived 17beta-estradiol equivalents toward estrogen receptor beta were 21 +/- 4-fold and 40 +/- 10-fold higher than the 17beta-estradiol concentrations in adipose (0.283 +/- 0.089 pmol/g, P < 0.001) and glandular (0.246 +/- 0.091 pmol/g, P = 0.001) fractions, respectively.
CONCLUSION
After intake of soy milk and soy supplements, isoflavones reach exposure levels in breast tissue at which potential health effects may occur.
Topics: Adipose Tissue; Adolescent; Adult; Breast; Chromatography, Liquid; Dietary Supplements; Estradiol; Estrogen Receptor beta; Female; Genistein; Humans; Isoflavones; Mammary Glands, Human; Middle Aged; Phytoestrogens; Plant Extracts; Reference Values; Soy Foods; Glycine max; Tandem Mass Spectrometry; Tissue Distribution; Young Adult
PubMed: 20164315
DOI: 10.3945/ajcn.2009.28854 -
Journal of Bone and Mineral Research :... May 2004The soy phytoestrogen daidzein has biphasic dose responses, but the underlying mechanisms are not yet clear. Transcriptional and biochemical data show that PPARs, in...
UNLABELLED
The soy phytoestrogen daidzein has biphasic dose responses, but the underlying mechanisms are not yet clear. Transcriptional and biochemical data show that PPARs, in addition to ERs, are molecular targets of daidzein, which divergently regulates osteogenesis and adipogenesis. Dose responses are the result of a balance among PPARs and between ERs and PPARs.
INTRODUCTION
Soy phytoestrogens have been used for the purposes of treatment and prevention of osteoporosis. Biphasic dose responses of daidzein, one of the main soy phytoestrogens, have long been recognized, but the underlying molecular mechanisms of action are not yet clear.
MATERIALS AND METHODS
Mouse bone marrow cells and mouse osteoprogenitor KS483 cells that concurrently differentiate into osteoblasts and adipocytes were cultured. Biochemical measurement of alkaline phosphatase (ALP) activity, RT-PCR, and gene reporter assays were used in this study.
RESULTS
Daidzein, one of the major soy phytoestrogens, had biphasic effects on osteogenesis and adipogenesis. Daidzein stimulated osteogenesis (ALP activity and nodule formation) and decreased adipogenesis (the number of adipocytes) at concentrations below 20 microM, whereas it inhibited osteogenesis and stimulated adipogenesis at concentrations higher than 30 microM. When estrogen receptors (ERs) were blocked by ICI182,780, daidzein-induced effects were not biphasic. A decrease in osteogenesis and an increase in adipogenesis were observed at the concentrations higher than 20 and 10 microM, respectively. In addition to ERs, daidzein transactivated not only peroxisome proliferator-activate receptor gamma (PPARgamma), but also PPARalpha and PPARdelta at micromolar concentrations. Activation of PPARalpha had no direct effects on osteogenesis and adipogenesis. In contrast, activation of PPARdelta stimulated osteogenesis but had no effects on adipogenesis, whereas PPARgamma inhibited osteogenesis and stimulated adipogenesis. Transfection experiments show that an activation of PPARalpha or PPARgamma by daidzein downregulated its estrogenic transcriptional activity, whereas activation of PPARdelta upregulated its estrogenic transcriptional activity. Activation of ERalpha or ERbeta by daidzein downregulated PPARgamma transcriptional activity but had no influence on PPARalpha or PPARdelta transcriptional activity.
CONCLUSIONS
Daidzein at micromolar concentrations concurrently activates different amounts of ERs and PPARs, and the balance of the divergent actions of ERs and PPARs determines daidzein-induced osteogenesis and adipogenesis.
Topics: Adipocytes; Alkaline Phosphatase; Animals; Calcification, Physiologic; Cell Line; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal; Isoflavones; Mice; Osteoblasts; Osteogenesis; RNA, Messenger; Receptors, Cytoplasmic and Nuclear; Receptors, Estrogen; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transfection
PubMed: 15068509
DOI: 10.1359/JBMR.040120 -
Individual and combined soy isoflavones exert differential effects on metastatic cancer progression.Clinical & Experimental Metastasis Oct 2010To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of...
To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein (GFP) tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg/kg body weight (BW) or a combination of genistein (10 mg/kg BW), daidzein (9 mg/kg BW), and glycitein (1 mg/kg BW) three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase (PI3-K) pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10/84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9/84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis.
Topics: Animals; Blotting, Western; Cell Line, Tumor; Disease Progression; Female; Genistein; Humans; Isoflavones; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Reverse Transcriptase Polymerase Chain Reaction; Glycine max
PubMed: 20517637
DOI: 10.1007/s10585-010-9336-x -
Genetics and Molecular Research : GMR Jun 2016Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer...
Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer activity. However, the mechanisms through which daidzein affects osteoblast function have not been investigated thoroughly. Here, we show that daidzein stimulated cell proliferation and differentiation of osteoblasts, demonstrated by upregulation of XTT activity, enhancement of alkaline phosphatase (ALP) activity, and upregulation of osteoblast-specific marker genes, including Runt-related transcription factor 2 (Runx2) and Smad1, as well as upregulation of Runx2 and Smad1 protein expression. To determine the mechanisms underlying daidzein's effects on osteoblast differentiation, we first tested the role of daidzein in bone morphogenetic protein (BMP)-2 gene expression in OCT1 cells, and found that it significantly upregulated the expression of BMP-2. Furthermore, it significantly enhanced the phosphorylated protein level of Smad1/5/8 and the protein level of Osterix and increased the activity of 12xSBE-OC-Luc. Finally, we demonstrated that daidzein stimulated Col I, Runx2, and ALP expression, while these effects were significantly blocked by the BMP signaling inhibitor noggin. Together, our data indicate that daidzein acts through stimulating the activation of BMP-2/Smads pathway to promote osteoblast proliferation and differentiation.
Topics: Animals; Bone Morphogenetic Protein 2; Cell Differentiation; Cell Proliferation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Isoflavones; Mice; Octamer Transcription Factor-1; Osteoblasts; Phytoestrogens; Smad Proteins; Up-Regulation
PubMed: 27420978
DOI: 10.4238/gmr.15028792