Disease relevance of NSC 5112

• Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein [1].
• The present study was designed to determine if a diet enriched in the phytoestrogen isoflavones, genistin and daidzin, would alter the antigen-induced cellular infiltration, particularly eosinophilia, characteristic of a guinea pig model of asthma [2].
• RESULTS: In male SCID mice orthotopically implanted with the androgen-sensitive human prostate cell line LNCaP, dietary supplements of soy protein, genistin, and SPC reduced primary tumor weight by 42% (P = 0.07), 57% (P < 0.05) and 70% (P < 0.005), respectively [3].
• Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epidemiological findings [4].
• The enzymatic modification of genistin to enhance its water solubility was studied using two glycosyltransferases, cyclodextrin glucanotransferase from alkalophilic Bacillus sp. I-5 and 4-alpha-glucanotransferase from Thermus scotoductus [5].

High impact information on NSC 5112

• Mice treated with genistin and SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo [6].
• Pure soy isoflavones (genistein, genistin, daidzein, and biochanin A) and soy phytochemical concentrate exhibit dose-dependent growth inhibition of murine (MB49 and MBT-2) and human (HT-1376, UM-UC-3, RT-4, J82, and TCCSUP) bladder cancer cell lines, although the degree of inhibition varies among lines [7].
• Furthermore, genistein, but not genistin, antagonized both the phosphorylation of JAK2 and the suppression of Glu release induced by EPO and EMP1 [8].
• Genistein (100 microM) completely blocked [Ca2+]i responses to 10(-8) M IL-1, whereas its inactive analogue genistin was not inhibitory [9].
• Electrospray ionization mass spectrometry was used to detect daidzin and genistin after solid-phase extraction of these conjugates from plasma [10].

Biological context of NSC 5112

• Dietary genistin resulted in increased tumor growth, pS2 expression and cellular proliferation similar to that observed with genistein [1].
• In a limited study of 17 subjects, the interindividual variability in the hydrolysis of genistein 7-glucoside was >20-fold [11].
• Results suggest that if sufficient circulating concentrations are reached in tissues of animals consuming soy products, genistein/genistin can potentially affect normal muscle growth and development [12].
• Uptake and intestinal metabolism of physiologically active genistin were studied in an ex vivo intestinal perfusion model; luminally applied concentrations were 5.9, 12.0, and 23.8 micromol/l. The intestinal absorption of genistin was 14.9% (+/-2.3, n=9), irrespective of the amounts applied [13].
• A total of 75 patients in natural or surgical menopause suffering from at least seven hot flushes per day were randomized to receive during 4 months either soy isoflavone extract (total of 70 mg genistin and daidzin per day) or placebo [14].

Anatomical context of NSC 5112

• Next, we examined how effectively and where metabolism of genistin to genistein occurred in the digestive tract [1].
• Absorption and metabolism of genistin in the isolated rat small intestine [13].
• Genistein or genistin inhibited protein accretion in myotubes (P < 0.001) [12].
• Genistein or genistin strongly inhibited in vitro myoblast proliferation (P < 0.001) and fusion (P < 0.001) in a dose-dependent manner with effective genistein concentration as low as 1 micromol/L [12].
• Here we report the vascular effects of the extract and purified genistin and kaempferol glycosides on contractions induced by different constricting agonists in isolated rat carotid arteries [15].

Associations of NSC 5112 with other chemical compounds

• The Km for hydrolysis of quercetin 4'-glucoside and genistein 7-glucoside was approximately 32+/-12 and approximately 14+/-3 microM in both tissues respectively [16].
• Phloridzin improves absorption of genistin in isolated rat small intestine [17].
• For this reason genistein, daidzein, genistin, and osajin (a diprenyl-genistein derivative) were incorporated into SDS micelles (in D(2)O) to evaluate differences in position and orientation within micelle structures [18].
• Seeds of the five soybean genotypes studied consistently stored most of their isoflavones as glucosyl conjugates (e.g., daidzin, genistin, and puerarin) [19].
• We also found that genistin, a baicalin derivative known to be antimutagenic, more selectively inhibited TdT activity than baicalin, although its IC50 value was weaker (28.7 microM) [20].

Gene context of NSC 5112

• The relative expression of pS2, progesterone receptor and cyclin D1 was increased in animals consuming the Novasoy(R), mixed isoflavones and genistin [21].
• Genistin showed inhibitory effects on IL-5 and IL-3 bioactivities, but did not inhibit GM-CSF and IL-6 bioactivities [22].
• The aim of this study was to investigate the effect of phloridzin, an inhibitor of the sodium-dependent glucose transporter (SGLT1), on genistin absorption and metabolism [17].
• The temperature dependence of genistin loss followed the Arrhenius relation with activation energies of 7.2 kcal/mol at ambient temperatures and 17.6 kcal/mol at elevated temperatures [23].
• Genistin has antioxidant activities; however, its insolubility in water often limits its biological availability in vivo [24].

Analytical, diagnostic and therapeutic context of NSC 5112

• The soy isoflavones daidzin, glycitin, and genistin were purified from defatted soy flour using preparative-scale reverse-phase HPLC [25].
• However, equimolar oral administration of genistin did not induce thymus atrophy [26].

References