Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis.

Abstract

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.

• Authors: Virgilo A Salvo, Stephen M Boué, Juan P Fonseca, Steven Elliott, Cynthia Corbitt, Bridgette M Collins-Burow, Tyler J Curiel, Sudesh K Srivastav, Betty Y Shih, Carol Carter-Wientjes, Charles E Wood, Paul W Erhardt, Barbara S Beckman, John A McLachlan, Thomas E Cleveland, Matthew E Burow
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 23 Pg. 7159-64 (Dec 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 17145841 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Benzopyrans
• Estrogen Receptor Modulators
• Pterocarpans
• Receptors, Progesterone
• Estradiol
• glyceollin

Topics

• Animals
• Benzopyrans (administration & dosage, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Estradiol (administration & dosage)
• Estrogen Receptor Modulators (administration & dosage, chemistry, pharmacology)
• Female
• Humans
• Mice
• Mice, Nude
• Ovarian Neoplasms (drug therapy, pathology)
• Predictive Value of Tests
• Pterocarpans
• Receptors, Progesterone (biosynthesis, drug effects)
• Structure-Activity Relationship
• Transplantation, Heterologous
• Uterus (drug effects, pathology)
• Xenograft Model Antitumor Assays