Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis

Clin Cancer Res. 2006 Dec 1;12(23):7159-64. doi: 10.1158/1078-0432.CCR-06-1426.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

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