Docket Number: 9508
Serial Number: 12082583

Summary: The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their hormonal activity and 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 health benefits of soy may therefore be dependent upon the amounts of the various hormonally active phytochemicals present. We have identified increased biosynthesis of the isoflavonoid phytoalexin compounds, Glyceollins I, II and III, in soy plants grown under stressed conditions (elicited soy), which exhibit marked anti-estrogenic effects on ER function. Here we demonstrate that specific glyceollins, isolated from elicited soy, displayed anti-estrogenic activity, suppressing basal and estrogen stimulated colony formation of ER-positive estrogen dependent breast cancer cells and inhibiting ER-dependent gene expression of progesterone receptor (PgR) and stromal derived factor-1 (SDF1/CXCL12). Examining the effects of glyceollin on in vivo tumor formation/growth we demonstrate the ability of glyceollins to significantly suppress basal and estrogen-stimulated tumor growth of ER-positive MCF-7 breast and BG-1 ovarian carcinoma cells in ovariectomized female nude mice. We further demonstrate that the effects of glyceollins on suppression of tumor growth correlate with inhibition of estrogen stimulated PgR expression. In contrast to the uterotropic activity of tamoxifen the glyceollins displayed no uterine agonist activity. The Glyceollin (I-III) compounds may represent an important component of the health effects of soy as well as represent novel anti-estrogens useful in the prevention or treatment of breast and ovarian carcinoma. Patent Status: Patent Application Filed on April 11, 2008. Link at USPTO filed under patent title “Antiestrogenic glyceollins suppress human breast and ovarian carcinoma proliferation and tumorigenesis.” Inventors: Thomas E Cleveland Southern Regional Research Center (New Orleans, La) 1100 ROBERT E. LEE BLVD NEW ORLEANS, LA, 70179 Phone: (504) 286-4214 Fax: (504) 286-4234 Ed.Cleveland@ars.usda.gov Matthew Burow Tulane Center for Bioenvironmental Research New Orleans, LA Stephen M Boue Food and Feed Safety Research 1100 ROBERT E. LEE BLVD. BLDG 001 SRRC NEW ORLEANS, LA, 70124 Phone: (504) 286-4346 Fax: (504) 286-4419 Steve.Boue@ars.usda.gov John McLachlan Tulane Center for Bioenvironmental Research New Orleans, LA