Antiestrogenic glyceollins suppress human breast and ovarian carcinoma proliferation and tumorigenesis

US8323706B2 · kind B2 · utility

Assignees

• The United States of America, as represented by the Secretary of Agriculture · US
• Tulane Educational Fund · US

Inventors

• Thomas Cleveland · San Diego, US
• Stephen M. Boue · New Orleans, US
• Matthew E. Burow · New Orleans, US
• John A. McLachlan · New Orleans, US

Key dates

• Filing date: Apr 11, 2008
• Grant date: Dec 4, 2012
• Expiry date: Sep 9, 2028

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 …