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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #227768

Title: Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP

Author
item PAYTON-STEWART, F - Tulane University
item Schoene, Norberta
item KIM, YOUNG - NCI
item BURROW, M - Tulane University
item CLEVELAND, THOMAS - SRRC,USDA
item BOUE, S - Tulane University
item Wang, Thomas - Tom

Submitted to: Molecular Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/22/2009
Publication Date: 4/22/2009
Citation: Payton-Stewart, F., Schoene, N.W., Kim, Y.S., Burrow, M.E., Cleveland, T.E., Boue, S.M., Wang, T.T. 2009. Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP. Molecular Carcinogenesis. 48(9):862-871.

Interpretive Summary: Soy contains several phytochemicals that may be responsible for its purported cancer protective effects. Glyceollins are soy–derived phytoalexins that have been proposed to be candidate cancer-preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexins, glyceollins, on the cultured human prostate cancer cell LNCaP to further elucidate potential effects on prostate cancer prevention. We found that the glyceollins inhibited LNCaP cell growth similar to that of the soy isoflavone genistein. The growth inhibitory effects of the glyceollins appeared to be due to an inhibition of progression through the cell cycle and correlated with an increase in a key message for cell signaling. By contrast, genistein only increased a more select set of messages. In addition, the glyceollin treatment also led to a decreased message for androgen-responsive genes. In contrast to genistein, this effect of glyceollins on androgen responsive genes appeared to occur through an estrogen- but not androgen-mediated pathway. Hence, the glyceollins exerted multiple effects on LNCaP cells that may be considered cancer preventive, and the mechanisms of action appear to be different from other soy-derived phytochemicals. This work provides novel information for cancer research scientists regarding molecular targets and mechanism(s) of action of soy-derived phytochemical(s) and will serve as an important basis for future investigation of targets of cancer cell growth and signaling. This work will benefit basic as well as translational research science.

Technical Abstract: Glyceollins are soy–derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexins, glyceollins, on the human prostate cancer cell line LNCaP to further elucidate its potential effects on prostate cancer prevention. We found that the glyceollins inhibited LNCaP cell growth similar to that of the soy isoflavone genistein. The growth inhibitory effects of the glyceollins appeared to be due to an inhibition on G1/S progression and correlated with an up-regulation of cyclin-dependent kinase inhibitor A1 and B1 mRNA levels. By contrast, genistein only up-regulates cyclin-dependent kinase inhibitor A1. In addition, the glyceollin treatments led to down-regulated androgen-responsive gene mRNA levels. In contrast to genistein, this effect of glyceollins on androgen responsive genes appeared to be mediated through modulation of an estrogen- but not androgen-mediated pathway. Hence, the glyceollins exerted multiple effects on LNCaP cells that may be considered cancer preventive and the mechanisms of action appeared to be different from other soy-derived phytochemicals.