ANTIESTROGENIC GLYCEOLLINS SUPPRESS HUMAN BREAST AND OVARIAN CARCINOMA TUMORIGENESIS

Authors: SALVO, VIRGILO - TULANE UNIV HEALTH SC CTR; Boue, Stephen; FONSECA, JUAN - TULANE UNIV HEALTH SC CTR; ELLIOTT, STEVEN - TULANE UNIV HEALTH SC CTR; CORBITT, CYNTHIA - UNIV OF LOUISVILLE, KY; COLLINS-BUROW, BRIDGETTE - TULANE UNIV HEALTH SC CTR; CURIEL, TYLER - TULANE UNIV HEALTH SC CTR; SRIVASTAV, SUDESH - Tulane University Medical Center; Shih, Betty; Carter-Wientjes, Carol; WOOD, CHARLES - WAKE FOREST UNIV SC MED; ERHARDT, PAUL - UNIV OF TOLEDO, OH; BECKMAN, BARBARA - TULANE UNIV HEALTH SC CTR; MCLACHLAN, JOHN - TULANE UNIV HEALTH SC CTR; Cleveland, Thomas; BUROW, MATTHEW - TULANE UNIV HEALTH SC CTR

Submitted to: Clinical Cancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2006
Publication Date: 11/30/2006
Citation: Salvo, V.A., Boue, S.M., Fonseca, J.P., Elliott, S., Corbitt, C., Collins-Burow, B.M., Curiel, T.J., Srivastav, S.K., Shih, B.Y., Carter-Wientjes, C.H., Wood, C.E., Erhardt, P.W., Beckman, B.S., Mclachlan, J.A., Cleveland, T.E., Burow, M.E. 2006. Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis. Clinical Cancer Research. 12(23):7159-7164.

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 unkown health effects (beneficial or harmful) in animals. We have identified the phytoalexin compounds, glyceollins I, II and III, which exhibit marked anti-estrogenic effects on estrogen receptor (ER) function and estrogen-dependent tumor growth in vivo. We investigated interactions between the induced soy phytoalexins glyceollins I, II, and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1 ovarian cancer cells implanted in female mice. Treatment with glyceollin suppressed tumor growth of MCF-7 cells and BG-1 cells in female mice. In contrast to tamoxifen, the glyceollins had no harmful effects on the uterine. These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.

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 aim of this study was to identify unique soy phytochemicals that had not been previously assessed for estrogenic or antiestrogenic activity. We have identified the phytoalexin compounds, glyceollins I, II and III, which exhibit marked anti-estrogenic effects on estrogen receptor (ER) function and estrogen-dependent tumor growth in vivo. We investigated interactions between the induced soy phytoalexins glyceollins I, II and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1 ovarian cancer cells implanted in ovariectomized athymic mice. Four treatment groups for each cell line were used: vehicle control; 20 mg/kg/mouse/day glyceollin mixture injection; 0.72 mg estradiol (E2) implant; and E2 implant + 20 mg/kg/mouse/day glyceollin injection. Treatment with glyceollin suppressed E2-stimulated tumor growth of MCF-7 cells (-53.4%) and BG-1 cells (-73.1%) in ovariectomized athymic mice. These tumor-inhibiting effects corresponded with significantly lower E2-induced progesterone receptor expression in the tumors. In contrast to tamoxifen, the glyceollins had no estrogen-agonist effects on uterine morphology and partially antagonized the uterotropic effects of estrogen. These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.