Genistein

Genistein is an ATP competitive inhibitor. Genistein inhibits tyrosine phosphorylation in isolated enzyme and receptor preparations and in whole cells including platelets, lymphocytes and a variety of cultured cells. It also inhibits EGF-stimulated phosphorylation in cultured cells as well as inhibition of Topo II (topoisomerase II). Genistein inhibits EGF-stimulated tyrosine phosphorylation in cultured A431 epidermoid carcinoma cells. Inhibition is competitive with ATP and noncompetitive with substrate. ^[1] Genistein blocks the mitogenic effect mediated by EGF and thrombin on NIH-3T3 cells.^[2] Genistein also acts as an agonist at the GPR30 receptor and binds to PPARγ and estrogen receptors. Genistein also binds to PPARγ, acting as an agonist at this receptor with K_i of 5.7 μM. ^[3]

Genistein has chemopreventive effects on breast, prostate, and other endocrine-dependent tumors in adult animals. Genistein in the diet reduced the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner and down-regulated androgen receptor, estrogen receptor-alpha, epidermal growth factor receptor, and extracellular signal-regulated kinase-1 but not estrogen receptor-beta and transforming growth factor-alpha mRNA expressions. Dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways.^[4] Genistein combined with prostate tumor irradiation causes greater inhibition of primary tumor growth and increases control of spontaneous metastasis to para-aortic lymph nodes, increasing mouse survival. Paradoxically, treatment with genistein alone increases metastasis to lymph nodes. ^[5]