Disease relevance of C00799

• When these genes were expressed in Escherichia coli, A411 had no spermidine synthase activity but did show putrescine N-methyltransferase activity, which is the first enzyme committed to the nicotine biosynthetic pathway, and A622 did not show isoflavone reductase activity [1].
• The use of dietary isoflavone supplements by postmenopausal women with breast cancer is increasing [2].
• Genistein, the most abundant isoflavone present in soybean has antiproliferative effects on a variety of cancer cells, including prostate cancer [3].
• We also evaluated both genistin, which is a natural form of genistein, and the isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis of 253J B-V tumors in an orthotopic tumor model [4].
• Our results suggest that two of isoflavone derivatives, biochanin A and genistein, inhibit the cell growth of stomach cancer cell lines in vitro through activation of a signal transduction pathway for apoptosis [5].

Psychiatry related information on C00799

• Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases [6].
• Associations of plasma isoflavone concentrations with other dietary behaviors suggest that these compounds may serve as biomarkers of health behaviors in populations with low soy consumption [7].
• Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men [8].
• An experiment clarifying the influence of food deprivation on the isoflavone conjugation pattern in rats was conducted [9].
• This risk reduction has generally been presumed to be a consequence of increased isoflavone consumption [10].

High impact information on C00799

• We expressed soybean isoflavone synthase in Arabidopsis thaliana, which led to production of the isoflavone genistein in this nonlegume plant [11].
• However, isoflavone O-methyltransferase (IOMT) from alfalfa converts the isoflavone daidzein to 7-O-methyl daidzein (isoformononetin) in vitro as well as in vivo in unchallenged leaves of transgenic alfalfa ectopically expressing IOMT [12].
• Genetic manipulation of isoflavone 7-O-methyltransferase enhances biosynthesis of 4'-O-methylated isoflavonoid phytoalexins and disease resistance in alfalfa [12].
• The predicted polypeptide is highly homologous ( > 70%) to leguminous isoflavone reductases (IFRs), but the maize protein (IRL for isoflavone reductase-like) belongs to a novel family of proteins present in a variety of plants [13].
• A maize gene encoding an NADPH binding enzyme highly homologous to isoflavone reductases is activated in response to sulfur starvation [13].

Chemical compound and disease context of C00799

• We have demonstrated that the isoflavone, genistein, stimulates growth of estrogen-dependent human breast cancer (MCF-7) cells in vivo (C. Y. Hsieh et al., Cancer Res., 58: 3833-3838, 1998) [14].
• We investigated interactions between the soy isoflavone, genistein, and an antiestrogen, tamoxifen (TAM), on the growth of estrogen (E)-dependent breast cancer (MCF-7) cells implanted in ovariectomized athymic mice [2].
• Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption [15].
• Newly diagnosed breast cancer cases up to 1 January 2001 were identified through linkage with the Comprehensive Cancer Center Middle Netherlands. Hazard ratios for the disease were estimated by Cox proportional hazard analysis for quartiles of isoflavone and lignan intake [16].
• Increased urinary excretion of equol, a metabolite of the isoflavone daidzein, has been associated with a reduced risk of breast cancer [10].

Biological context of C00799

• Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells [17].
• Consumption of an isoflavone-containing soya diet reduced levels of ovarian steroids in normal women over the entire menstrual cycle without affecting gonadotropins [18].
• Genistein, a dietary isoflavone, down-regulates the MDM2 oncogene at both transcriptional and posttranslational levels [19].
• Its amino acid sequence reveals a strong homology to isoflavone reductase, a key branchpoint enzyme in isoflavonoid metabolism and primarily found in the Fabaceae (angiosperms) [20].
• The Isoflavone Equol Mediates Rapid Vascular Relaxation: Ca2+-INDEPENDENT ACTIVATION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE/Hsp90 INVOLVING ERK1/2 AND Akt PHOSPHORYLATION IN HUMAN ENDOTHELIAL CELL [21].

Anatomical context of C00799

• Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory mediators in human endothelial cells in vitro, and partially reduces the basal PAI-1 production by these cells [22].
• Plasma isoflavone concentrations reported previously for 4-mo-old infants fed soy-based formula were 654-1775 microg/L (mean: 979.7 microg/L: Lancet 1997:350;23-7), significantly higher than plasma concentrations of infants fed either cow-milk formula (mean +/- SD: 9.4 +/- 1.2 microg/L) or human breast milk (4.7 +/- 1.3 microg/L) [23].
• The recombinant enzymes in yeast microsomes utilized the same isoflavone substrates, but produced different products hydroxylated at the 2' and/or 3' positions of the B-ring [24].
• Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes [25].
• The possibility that the heightened cardiovascular risk associated with the menopause can be reduced by increasing dietary isoflavone intake was tested in 17 women by measuring arterial compliance, an index of the elasticity of large arteries such as the thoracic aorta [26].

Associations of C00799 with other chemical compounds

• The bottleneck for constitutive isoflavone production in Arabidopsis is, therefore, competition for flavanone between IFS and endogenous flavonol synthesis, and the flavonol pathway is reciprocally but disproportionately affected by IFS [27].
• Use of a mammalian cell culture benzo(a)pyrene metabolism assay for the detection of potential anticarcinogens from natural products: inhibition of metabolism by biochanin A, an isoflavone from Trifolium pratense L [28].
• Phenoxodiol, a novel isoflavone, induces G1 arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21WAF1/CIP1 [29].
• In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (>80%) showed no tumor formation by 60 weeks of age [30].
• Adult, surgically postmenopausal female macaques (Macaca fascicularis) were treated continuously with either estradiol (E2), an isoflavone-rich soy protein isolate (SPI), or both (E2+SPI) [31].

Gene context of C00799

• Both inhibitors decreased basal production of prostacyclin, but only COX-2 inhibition completely abolished the isoflavone-stimulated prostacyclin production [32].
• These data suggest an important interplay between the p38 pathway and G2 cell cycle checkpoint control and provide insights into possible mechanisms whereby this isoflavone may inhibit early events in mammary carcinogenesis [33].
• Thus, high levels of isoflavone intake appear to increase serum concentrations of IL-6 in women [34].
• CYP1A1 catalyzed isoflavone 4'-O-demethylation and hydroxylations with similar efficiency, whereas CYP1B1 favored 4'-O-demethylation over hydroxylations [35].
• In the present study, genistein was found to be an effective inhibitor of recombinant human CYP1A1 and CYP1B1 with Ki of 15.35 and 0.68 micromol/l. The other soya isoflavone daidzein, on the other hand, did not demonstrate any significant inhibition of the enzyme activities [36].

Analytical, diagnostic and therapeutic context of C00799

• The HPLC conditions for soy isoflavone analysis were improved, leading to good separation with a short analysis time (60 min/sample) [37].
• In 2 randomized, cross-over studies, 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [control, 0.13; low isoflavone (low-iso), 1.00; and high-iso, 2.01 mg/kg body wt/day, averaging 8, 65, and 130 mg/day, respectively], for over 3 months each [38].
• BACKGROUND: Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT) [39].
• DESIGN: In this cross-sectional study, soy isoflavone intake and plasma isoflavone concentration were analyzed in 96 postmenopausal women aged 50-79 y; the data were obtained at 2 visits that were 1 wk apart [7].
• OBJECTIVE: To assess the biological activity of isoflavone phytoestrogens, we analyzed the effect of dietary soy isoflavone supplementation on in vivo bioassays of estrogenicity [40].

References