Genistein activity

FRENCH p J, HUMAN J, HOT A G, BooMARS w E, SCHOLTE B J and D E JONGE H R (1997) Genistein activates CFTR Crchannels via a tyrosine kinase- and protein phosphatase-independent mechanism. dm J Physiol. 273 (2 Ptl) C747-C753. 

Goddard CA, Evans MJ, Colledge WH. 2000. Genistein activates CFTR-mediated Cl(—) secretion in the murine trachea and colon. Am J Physiol Cell Physiol 279 C383-392. 

Lamon-Fava, S., Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line Hep G2, J. Nutr., 130, 2489, 2000. 

MOERSCH G w, MORROW D F, NEUKLis w A (1967) The antifeitiUty activity of isoflavones related to genistein. J Afed Chem. 10 154-8. 

Gao and Yamaguchi, 1999c Gao and Yamaguchi, 2000 Kajiya et al., 2000 Yamagishi et at., 2001 Bone marrow cells or isolated osteoclasts Suppression of osteoclast formation by genistein is partly due to Ca signalling mechanism and partly due to inhibition of tyrosine kinase activity. 

Gao and Yamaguchi, 1999a Yamaguchi and Ma, 2001 Femoral-diaphyseal tissues from elderly female rats cultured for 24 h Daidzein or genistein (lO M, lO M) induced calcium content and alkaline phosphatase (ALP) activity indicating stimulation of bone formation. 

GAO Y H and YAMAGUCHI M (2000) Suppressive effect of genistein on rat bone osteoclasts Involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5, 261-7. 

YAMAGUCHI M and suGiMOTO E (2000) Stimulatory effect of genistein and daidzein on protein synthesis in osteoblastic MC3T3-E1 cells Activation of aminoacyl-tRNA synthetase. Mol Cell Biochem 214, 97-102. 

The mucosa of the GIT represents an interface between the external and internal environments. The expansive surface area is necessary for the efficient hydrolysis of foodstuffs and the absorption of energy and nutrients. The mucosa also influences the systemic availability of non-nutrient compounds in the diet, both beneficial and detrimental. Digestion and absorption of glucosinolates are critical determinants of health benefits (see Chapter 4) Similarly, the bioavailability and health benefits of phytoestrogens, such as genistein (see Chapters 5 and 10) are at least partly dependent on the carrier-mediated processes of absorption associated with the GIT (Oitate et al, 2001). Moreover, the metabolic activities of the mucosa can influence the systemic concentrations and forms of dietary phytochemicals, as exemplified by research with soy isoflavones (Andlauer et al., 2000). 

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

The mechanism of action proposed is based on a direct binding to the channel and the following partial block of the ATP-binding pocket of CFTR (French et al., 1997), a mechanism similar to that used by genistein to inhibit the activity of other ATP-utilizing enzymes such as protein kinases and topoisomerase II (Polkowski and Mazurek, 2000 and refs therein). The selection of flavonoid compounds or the development of synthetic drugs reasonably selective for CFTR activation might be an area for future clinical trials. 

ILLEK B, FISCHER H, SANTOS G F, WIDDICOMBE J H, MACHEN T E and REENSTRA W W (1995) cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein. ./Physiol. 268 (4 Ptl) C886-C893. 

LiNASSiER c, PIERRE M, LE PECQ J B and PIERRE J (1990) Mechanism of action in NIH-3T3 cells of genistein, an inhibitor of EGF receptor tyrosine kinase activity. Biochem Pharmacol. 39 (1) 187-93. 

ZHANG Y, SONG T T, CUNNICK J E, MURPHY p A and HENDRICH s (1999a) Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells in nutritionally relevant concentrations. /iVMr 129 (2) 399-405. 

King-Batoon et al. have found that the physiological concentrations of lycopene (2pM) partially demethylated the promoter for GSTP1 and restored its expression in the breast cancer cell line MDA-MB-468, but RAR0 was not demethylated. However, lycopene did induce the demethylation of RARp in MCF10A fibrocystic cells (King-Batoon et al. 2008). Genistein, in this study, was less active compared to lycopene. 

Hirsch, K, A Atzmon, M Danilenko, J Levy, and Y Sharoni. 2007. Lycopene and other carotenoids inhibit estrogenic activity of 17 beta-estradiol and genistein in cancer cells. Breast Cancer Res Treat 104 221-230. 

Hernandez-Montes E, Pollard SE, Vauzour D, Jofre-Montseny L, Rota C, Rimbach G, Weinberg PD and Spencer JPE. 2006. Activation of glutathione peroxidase via Nrfl mediates genistein s protection against oxidative endothelial cell injury. Biochem Biophys Res Commun 346(3) 851—859. 

Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E. 2007. Anti-inflammatory effects of flavonoids genistein, kaempferol, quercetin and daidzein inhibit STAT-1 and NF-kB activations whereas flavones, isorhamnetin, naringenins, and pelargonidin inhibit only NF-kB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophagues. Mediators Inflamm 2007 45673. 

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