Genistein action

Cotroneo MS, Wang J, Fritz WA, Eltoum IE, Lamartiniere CA. Genistein action in the prepubertal mammary gland in a chemoprevention model. Carcinogenesis 23, 1467-1474, 2002. 

Bancajee S, Zhang Y, Wang Z, Che M, Chiao PJ, Abbnizzese JL, Sarkar FH (2007) In vitro and in vivo molecular evidence of genistein action in augmenting the efficacy of cisplatin in pancreatic cancel. Int J Cancer 120 906-917... 

CONSTANTINOU A, HUBERMAN E (1995) Genistein as an inducer of tumour cell differentiation possible mechanisms of action. Proc Soc Exp Biol Med. 208 109-15. 

In addition to the effects on blood lipids, it has been suggested that soy consumption has a beneficial action on arterial function and improves antioxidant status (Lichtenstein, 1998 and refs therein). Genistein and daidzein were shown to have antioxidant properties in vitro (Kerry and Abbey, 1998), to enhance endothelium-dependent vasodilation and to reduce the development of atherosclerosis in monkeys (Honore et al, 1997 Wagner et al, 1997). 

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. 

KIM H, PETERSON T G and BARNES s (1998) Mechanism of action of the soy isoflavone genistein emerging role for its effects via transforming growth factor 3 signalling pathways. J Clin Nutr. 68 (6 Suppl) 1418S-1425S. 

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. 

WEINREICH F, WOOD p G, RiORDAN J R and N AGEL G (1997) Direct action of genistein on CFTR. Pfluegers Arch. 434 (4) 484-91. 

Baluchnejadmojarad T, Roghani M. (2008) Chronic administration of genistein improves aortic reactivity of streptozotocin-diabetic rats Mode of action. Vascul Pharmacol 49 1-5. 

Kim H, Xu J, Su Y et al. Actions of the soy phytoestrogen genistein in models of human chronic disease potential involvement of transforming growth factor p. Biochem. Soc. Trans. 29, 216-222, 2001. 

Chu L, Zhang JX, Norota I, Endoh M. 2005. Differential action of a protein tyrosine kinase, inhibitor genistein, on the positive inotropic effect of endothelin-1 and norepinephrine in canine ventricular myocardium. Br J Pharmacol 144 430-442. 

Valero MS, Garay RP, Gros P, Alda JO. 2006. Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and Na-K-Cl cotransporter NKCC1 isoform mediate the vasorelaxant action of genistein in isolated rat aorta. Eur J Pharmacol 544 126-131. 

Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A. 2002. Genistein chemoprevention Timing and mechanisms of action in murine mammary and prostate. J Nutr 132 552S-558S. 

T lymphocyte Kvl.3 potassium channels were also inhibited by genistein (42) in a protein tyrosine kinase (PTK)-independent way [290]. Daidzein (40) that was also studied in this work did not influence the properties of Kvl.3 potassium channels. The genistein-induced inhibition occurred much faster than was observed for neuronal Kvl.3 channels expressed in HEK293 cells [291], for which a PTK-dependent mechanism of genistein (42) action was proposed. On the other hand, PTK-independent inhibition of myocyte Kvl.3 channels by genistein (42) was reported by Washizuka et al. [292]. 

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