Potential Therapeutic Use of Glyceollins (I-III), Novel Anti-Estrogenic Flavonoid Phytochemicals Isolated From Soy

摘要

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 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 II, in soy plants grown under stressed conditions (elicited soy) which exhibit marked anti- estrogenic effects on ER function. 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 carcinoma. in this grant we propose to test the hypothesis that elicited soy extract, which has been shown to be anti-estrogenic in cell culture, is therapeutic in a tumor-transfer model of breast cancer. Using this model, we additionally hypothesize that specific Glyceollins, isolated from elicited soy, will display anti-estrogenic activity in vivo, suppressing the growth of breast tumors. To this end in the first year of this proposal we have, (1) completed preliminary studies establishing the MCF- 7 in vivo immunocompromised mouse model of tumorigenesis in this lab; (2) generated and 110 Kg of elicited soybeans to be converted to protein for use in the mouse soy diet studies and confirmed Glyceollin expression in various products; (3) begun separation of individual Glyceollins (I,II,III) from purified Glyceollin (I, II, III) mixture; (4) established the in vitro suppression of colony formation (survival/proliferation) by Glyceollins; and (5) demonstrated suppression of estrogen stimulated VEGF expression by Glyceollins.