|Burow, Matthew - TULANE UNIVERSITY|
|Collins-Burow, Bridgette - TULANE UNIVERSITY|
|Melnik, Lilia - TULANE UNIVERSITY|
|Duong, Bich - TULANE UNIVERSITY|
|Li, Shuanfang - TULANE UNIVERSITY|
|Wiese, Thomas - TULANE UNIVERSITY|
|Mclachlan, John - TULANE UNIVERSITY|
Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 7, 2000
Publication Date: April 1, 2001
Citation: Burow, M.E., Boue, S.M., Collins-Burow, B.M., Melnik, L.I., Duong, B.N., Carter Wientjes, C.H., Li, S., Wiese, T.E., Cleveland, T.E., Mclachlan, J.A. 2001. Phytochemical glyceollins, isolated from soy, mediate anti-hormonal effectsthrough estrogen receptor alpha and beta. Journal of Clinical Endocrinology and Metabolism. 86(4):1750-1758. Interpretive Summary: Studies have shown that dietary estrogens from plant sources (phytoestrogens) may play a role in the prevention of breast and prostate cancer. Soybean has become the main focus of study due to the high concentration of phytoestrogens present. Soybean seed contains several phytoestrogens, however the seed under conditions of stress produces several compounds called glyceollins with unknown health effects (beneficial or harmful) in animals. This study explores the possibility that the glyceollins may act as phytoestrogens. In this report it was found that the glyceollins were weak estrogens, however the glyceollins blocked the cancer cell growth effects of the female hormone estrogen. This study indicates that the glyceollins obtained from stressed soybean need to be considered when measuring the total phytoestrogen content of soybean. This research will benefit human health in general and will lead to a better understanding of the role of phytoestrogens in the prevention of certain cancers.
Technical Abstract: The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their estrogenic activity, as well as their effects on human health and disease. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The aim of this study was to identify unique soy phytochemicals that had not been previously assessed for estrogenic or antiestrogenic activity. Here we describe increased biosynthesis of the isoflavonoid phytoalexin compounds, glyceollins, in soy plants grown under stressed conditions. In contrast to the observed estrogenic effects of coumestrol, daidzein and genistein, we observed a marked antiestrogenic effect of glyceollins on ER signaling, which correlated with a comparable suppression of 17b-estradiol (E2)-induced proliferation in MCF-7 cells. Further evaluation revealed greater antagonism towards ERa than ERb in transiently transfected HEK 293 cells. Competition binding assays revealed a greater affinity of glyceollins for ERa versus ERb, that correlated to greater suppression of ERa signaling with higher concentrations of glyceollins. In conclusion, we describe the phytoalexin compounds known as glyceollins, that exhibit unique antagonistic effects on ER in both HEK 293 and MCF-7 cells.