Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis.
OBJECTIVE
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.


METHODS
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.
Salvo
Virgilo A
VA
Section of Hematology and Medical Oncology, Department of Medicine, Tulane Cancer Center, New Orleans, LA 70112, USA.
Boué
Stephen M
SM
Fonseca
Juan P
JP
Elliott
Steven
S
Corbitt
Cynthia
C
Collins-Burow
Bridgette M
BM
Curiel
Tyler J
TJ
Srivastav
Sudesh K
SK
Shih
Betty Y
BY
Carter-Wientjes
Carol
C
Wood
Charles E
CE
Erhardt
Paul W
PW
Beckman
Barbara S
BS
McLachlan
John A
JA
Cleveland
Thomas E
TE
Burow
Matthew E
ME
D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D036343:Pterocarpans; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D001578:Benzopyrans; D020847:Estrogen Receptor Modulators; D036343:Pterocarpans; D011980:Receptors, Progesterone; D004958:Estradiol; C017343:glyceollin