Isoflavone-induced activation of the extracellular signal-regulated kinase (ERK1/2) in non-tumorigenic prostate epithelial cells

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Epidemiological and experimental evidence suggests that increased consumption of soy is associated with a reduced risk for prostate cancer. Soy isoflavones are thought to be responsible, in part, for this anticancer activity. The present study evaluated the ability of four isoflavones (genistein, daidzein, glycitein, and equol) to modulate extracellular signal-regulated kinase (ERK1/2) activity in a non-tumorigenic prostate epithelial cell line (RWPE-1). ERK1/2 controls cellular proliferation and differentiation; however, the specific role of ERK1/2 signaling in prostate carcinogenesis remains unknown. Treatment of cells with genistein, daidzein, equol, and glycitein (10µM) increased ERK1/2 activity 7.2, 7.3, 12.3, and 47-fold respectively (p<0.05). Isoflavone-induced ERK1/2 activation was both time and concentration dependent. Further characterization of glycitein-induced ERK1/2 activation suggests involvement of vascular endothelial growth factor receptor tyrosine kinase activity. Interestingly, isoflavone-induced ERK1/2 activity was non-detectable in the highly malignant PC-3 prostate epithelial cell line. These data suggest that glycitein, despite its relatively low abundance, is a potent activator of the ERK1/2 signaling cascade in prostate epithelial cells.



Prostate, Soy isoflavones