Glycitein activates extracellular signal-regulated kinase via vascular endothelial growth factor receptor signaling in nontumorigenic (RWPE-1) prostate epithelial cells.
Increased consumption of soy is associated with a decreased risk for prostate cancer; however, the specific cellular mechanisms responsible for this anticancer activity are unknown. Dietary modulation of signaling cascades controlling cellular growth, proliferation and differentiation has emerged as a potential chemopreventive mechanism. The present study examined the effects of four soy isoflavones (genistein, daidzein, glycitein and equol) on extracellularsignal-regulated kinase (ERK1/2) activity in a nontumorigenic prostate epithelial cell line (RWPE-1). All four isoflavones (10 micromol/L) significantly increased ERK1/2 activity in RWPE-1 cells, as determined by immunoblotting. Isoflavone-induced ERK1/2 activation was rapid and sustained for approximately 2 h posttreatment. Glycitein, the most potent activator of ERK1/2, decreased RWPE-1 cell proliferation by 40% (P<.01). Glycitein-induced ERK1/2 activation was dependent, in part, on tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR). The presence of both VEGFR1 and VEGFR2 in the RWPE-1 cell line was confirmed by immunocytochemistry. Treatment of RWPE-1 cells with VEGF(165) resulted in transient ERK1/2 activation and increased cellular proliferation. The ability of isoflavones to modulate ERK1/2 signaling cascade via VEGFR signaling in the prostate may be responsible, in part, for the anticancer activity of soy.
Clubbs
Elizabeth A
EA
OSU Interdisciplinary PhD Program in Nutrition, The Ohio State University, Columbus, OH 43210, USA.
Bomser
Joshua A
JA
D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D007529:Isoflavones; D048789:Phytoestrogens; C086566:glycitein; D040262:Receptors, Vascular Endothelial Growth Factor; D048052:Mitogen-Activated Protein Kinase 3