Disease relevance of genistein

• Inhibition of hyposmotic Erk activation by pertussis or cholera toxin, erbstatin, or genistein had no effect on the swelling-induced inhibition of proteolysis [1].
• The high excretion of genistein in urine of vegetarians and our present results suggest that genistein may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumors, by inhibiting neovascularization [2].
• Genistein, a natural product from soy, is a potent inhibitor of transthyretin amyloidosis [3].
• The benefits of using a nutraceutical such as genistein to treat orphan diseases such as the TTR amyloidoses include known oral bioavailability and safety data [3].
• Genistein also inhibits the amyloidogenesis of the most common familial amyloid polyneuropathy and familial amyloid cardiomyopathy mutations in TTR: V30M and V122I, respectively [3].
• In male SHR-SP, dietary genistein blunts NaCl-sensitive hypertension, and these effects may be regulated, in part, by the autonomic nervous system and/or metabolic mechanisms [4].
• Increasing levels of ERalpha in breast cancer cells results in a progressive increase in induction of PI-9 by genistein and in the cell's ability to evade killing by NK cells [5].

Psychiatry related information on genistein

• These data suggest that genistein is carcinogenic if exposure occurs during critical periods of differentiation [6].
• OBJECTIVE: The objective was to investigate the bioavailability of the soy isoflavones daidzein and genistein in American women with typical American dietary habits after ingestion of the aglycone or glucoside form of isoflavones [7].
• Furthermore, genistein, a specific inhibitor of tyrosine kinases, blocked recovery from scopolamine-induced amnesia by S14G-HN, suggesting that certain tyrosine kinase(s) are involved in the inhibitory function of S14G-HN in vivo [8].
• Since maternal care may affect offspring behaviors in adulthood, it is important to determine the potential for genistein to affect maternal behavior [9].
• Genistein significantly increased tumor cross-sectional area and tumor multiplicity but not the tumor incidence and latency period when compared with the vehicle treated group [10].

High impact information on genistein

• Phosphoamino acid analyses of 32P-labeled ISGF3 alpha proteins confirm that ISGF3 alpha proteins are directly tyrosine phosphorylated both in vitro and in vivo in response to interferon alpha, and this tyrosine phosphorylation can be inhibited by staurosporine and genistein [11].
• Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient [12].
• We show here that genistein, an inhibitor of protein tyrosine kinase, blocks VEGF induction [13].
• The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined [14].
• The TPK inhibitor genistein blocked PDGF induction of these events, including DNA synthesis, with the exception of receptor down regulation [15].

Chemical compound and disease context of genistein

• RESULTS: EGF dose dependently inhibited carbachol-stimulated aminopyrine uptake in a pertussis toxin-insensitive, genistein (tyrosine kinase inhibitor)--sensitive manner, with a maximal inhibitory effect (37.5% +/- 6.8%) achieved at 10(-7) mol/L [16].
• Tyrosine kinase-inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect [17].
• Soy isoflavone genistein exhibits growth inhibitory activity against human pancreatic cancer cell lines [18].
• We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol [19].
• Collectively, our results clearly suggest that genistein pretreatment inactivates NF-kappaB and may contribute to increased growth inhibition and apoptosis induced by cisplatin, docetaxel, and doxorubicin in prostate, breast, lung, and pancreatic cancer cells [20].

Biological context of genistein

• Inhibition of PLD activity by genistein or herbimycin A was associated with inhibition of phagocytosis of M. tuberculosis and OZ [21].
• BACKGROUND: Soy products contain high levels of genistein, a phytoestrogen that is a potent inhibitor of cell proliferation and angiogenesis [22].
• Third, internalization of lipase-enriched lipoproteins via syndecan-1 and of clustered IgGs via the chimera showed identical kinetics (t1/2 = 1 h) and identical dose-response sensitivities to cytochalasin B, which disrupts microfilaments, and to genistein, which inhibits tyrosine kinases [23].
• The regulation of secretion by cell volume is not mediated via changes in CCK receptor binding or protein kinase C. The increase of amylase release caused by hypotonicity was completely inhibited by cytochalasin B, colchicine, and genistein [24].
• The tyrosine kinase inhibitors herbimycin A or genistein blocked both the accumulation of 19 out of 20 signal transduction molecules and JNK- and ERK-mediated signaling [25].

Anatomical context of genistein

• Influence of genistein and daidzein on Brca1 protein levels in human breast cell lines [26].
• Interestingly, genistein, a tyrosine kinase inhibitor, and GFX or H-7, PKC inhibitors, abolished both VEGF-induced PKC activation and endothelial cell proliferation [27].
• Vasoactive intestinal peptide, forskolin, and genistein increase apical CFTR trafficking in the rectal gland of the spiny dogfish, Squalus acanthias. Acute regulation of CFTR trafficking in an intact epithelium [28].
• In rectal glands perfused under basal conditions without secretagogues, Cl- secretion was 151+/-65 microeq/h/g. Vasoactive intestinal peptide (VIP), forskolin, and genistein led to 10-, 6-, and 4-fold increases in Cl- secretion [28].
• Invadopodia reduced or lost YPP labeling after treatment of the cells with genistein, but adhesion plaques retained YPP labeling [29].

Associations of genistein with other chemical compounds

• PDGF-induced phosphotyrosine phosphorylations, including receptor autophosphorylation, were inhibited by genistein [15].
• PURPOSE: The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein [30].
• RESULTS: Linomide selectively inhibited mouse macrophage secretion of TNF-alpha but not of GM-CSF; however, thalidomide, pentoxifylline, and genistein inhibited the production of both cytokines [31].
• However, the latter compound as well as NAC, genistein, inhibition of JNK, or protein kinase C inhibited CD95 tyrosine phosphorylation, membrane trafficking, and DISC formation [32].
• Here we report the three-dimensional structure of the oestrogen receptor beta isoform (ERbeta) ligand-binding domain (LBD) in the presence of the phyto-oestrogen genistein and the antagonist raloxifene [33].
• Compared with placebo, genistein significantly reduced fasting glucose and insulin as well as homeostasis model assessment for insulin resistance after both 12 and 24 months of treatment [34].
• Competition experiments using various flavonoids of both aglycone and glucoside varieties suggested that this ABC-type transporter recognizes genistein and daidzein, another signaling compound in soybean root exudates, as well as other isoflavonoid aglycones as its substrates [35].

Gene context of genistein

• Pretreatment of the cells with genistein (a protein-tyrosine kinase inhibitor) decreased the bradykinin- but not the NGF-induced changes in both TH-Ser31 phosphorylation and ERK activity [36].
• In contrast to TNF-alpha-induced PAI-1 production, the transcription and synthesis of urokinase-type plasminogen activator (u-PA) was not inhibited by genistein [37].
• Genistein similarly inhibited c-jun expression in stromal cells exposed to IL-1 (500 U/mL) plus TNF-alpha (500 U/mL) [38].
• The size of aggregates formed at a high shear rate in the presence of 2B-rVWF was decreased by genistein, demonstrating the biologic relevance of pp125FAK [39].
• CD4(+) T-cell proliferation was completely restored by exogenous IL-2 or reversed by pertussis toxin, wortmannin, and genistein, suggesting the involvement of multiple partners in Lptn signaling [40].
• Our data indicated that Brca1 mutant cells were more sensitive to genistein than some other types of cancer cells, highlighting a good therapeutic potential of genistein for BRCA1-associated breast cancer [41].

Analytical, diagnostic and therapeutic context of genistein

• During stimulation with secretagogues, apical extension of CFTR immunofluorescence into the cell was reduced significantly to 3.24+/-0.08 micron by VIP, 4.08+/-0.13 by forskolin, and 3.19+/-0.1 by genistein (P < 0.001) [28].
• The GM-CSF production by the coculture was markedly inhibited by genistein and partially inhibited by Abs against interleukin-1 and tumor necrosis factor-alpha [42].
• Herbimycin and genistein reduced by 30% and 50%, respectively, the rise in [Ca2+]i caused by optimal ligation of mIgM, and they abolished it in cells activated by suboptimal ligation of mIgM [43].
• Isothermal titration calorimetry shows that genistein binds to TTR with negative cooperativity (K(d1) = 40 nM, K(d2) = 1.4 microM) [3].
• Analysis of individual colonies by cytogenetics and RT-PCR confirmed that genistein-induced increase in the percentage of nonleukemic progenitors was not due to suppression of BCR/ABL transcription [44].

References