Soy isoflavones and membrane steroid receptors: a new horizon

Abstract

Soy isoflavone's (especially genistein and daidzein) health effects have been studied for decades, while their mechanisms of action remain complex, involving modulation of gene expression and enzyme activity. Currently there is a need for refreshed approach in this field considering identification of isoflavone's new molecular target. The cell membrane constituents-mediated effects of soy isoflavones are worthy of special attention from the perspective of cancer metastasis or cardiovascular diseases management. Specifically, the expanding concept of membrane steroid receptors and rapid signaling from the cell surface may include the prominent role of these steroid-like compounds. We have shown in vitro that genistein inhibits LNCaP prostate cancer cells invasiveness by decreasing the membrane fluidity. This is complemented with genistein-caused immobilization of the androgen receptor containing membrane lipid rafts and down regulation of the androgen receptors/Akt signaling in mentioned metastatic prostate cancer cell line. On the other hand, it was observed that daidzein strongly couples with membrane estrogen receptors in adrenal medullary cells. At low doses (10 - 1000 nM) daidzein was found to stimulate catecholamine synthesis via extracellular signal-regulated kinase 1/2 or protein kinase A pathways, but at higher doses it inhibited catecholamine synthesis and secretion induced by acetylcholine. Given that catecholamine excess can contribute to the cardiovascular pathologies and that catecholamine lack may lead to depression, daidzein application promises to have a wide range of therapeutic effects. These data are supportive in development of the molecular pharmacotherapy pertinent to balanced soy isoflavone treatment of steroid-related malignancies as well as cardiovascular and psychiatric diseases.