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Antiestrogenic Glyceollins Suppress Human Breast and Ovarian Carcinoma Tumorigenesis

Authors' Affiliations: ¹ Section of Hematology and Medical Oncology, Department of Medicine; Departments of ² Surgery, ³ Pharmacology, and ⁴ Biostatistics; ⁵ The Tulane Cancer Center; and ⁶ The Center for Bioenvironmental Research, Tulane University Health Science Center; ⁷ Southern Regional Research Center, U.S. Department of Agriculture, New Orleans, Los Angeles; ⁸ Department of Biology, University of Louisville, Louisville, Kentucky; ⁹ Department of Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and ¹⁰ Center for Drug Design and Development, University of Toledo, Toledo, Ohio

Requests for reprints: Matthew E. Burow, Section of Hematology and Medical Oncology, Tulane University Medical School, 1430 Tulane Avenue SL-78, New Orleans, LA 70112. Phone: 504-988-6688; Fax: 504-988-5483; E-mail: mburow{at}tulane.edu.

Purpose: We have identified the phytoalexin compounds glyceollins I, II, and III, which exhibit marked antiestrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. The purpose of this study was to investigate the interactions among 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.

Experimental Design: Four treatment groups for each cell line were used: vehicle control, 20 mg/kg/mouse/d glyceollin mixture injection, 0.72 mg estradiol (E2) implant, and E2 implant + 20 mg/kg/mouse/d glyceollin injection.

Results: 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.

Conclusions: These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.

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