Cancer: Prostate, breast, ovarian
Action: Anti-estrogenic
Glyceollins are soy-derived phytoalexins isolated from activated soy ( Glycine max [(L.) Merr.] that have been proposed to be candidates for cancer-preventive compounds.
Prostate cancer
It has been found that the glyceollins inhibited prostate cancer cell LNCaP growth similar to that of the soy isoflavone genistein. The growth-inhibitory effects of the glyceollins appeared to be due to an inhibition of G1/S progression and correlated with an up-regulation of cyclin-dependent kinase inhibitor 1 A and B mRNA and protein levels. By contrast, genistein only up-regulates cyclin-dependent kinase inhibitor 1A.
In addition, glyceollin treatments led to down-regulated mRNA levels for androgen responsive genes. In contrast to genistein, this effect of glyceollins on androgen responsive genes appeared to be mediated through modulation of an estrogen- but not androgen-mediated pathway.
Hence, the glyceollins exerted multiple effects on LNCaP cells that may be considered cancer-preventive and the mechanisms of action appeared to be different from other soy-derived phytochemicals (Payton-Stewart et al., 2009).
Anti-estrogenic Effects; Breast Cancer, Ovarian Cancer
The phytoalexin compounds glyceollins I, II, and III have been identified to exhibit marked anti-estrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. 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 were studied. 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.
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 anti-estrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma (Salvo et al., 2006).
Anti-estrogenic Effects
The soybean plant under stress produces a mixture of glyceollins I, II, and III that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. In further in vitro studies, the glyceollin mixture exhibits potential anti-estrogenic, therapeutic activity preventing estrogen-stimulated tumorigenesis and displaying a differential pattern of gene expression from tamoxifen.
Glyceollin I was identified as the active anti-estrogenic component of the mixture. Ligand-receptor modeling (docking) of the isomers within the ERα ligand binding cavity demonstrated a unique type II anti-estrogenic confirmation adopted by glyceollin I, but not isomers II and III. Glyceollin I treatment in 17β- estradiol-stimulated MCF-7 breast cancer cells and BG-1 ovarian cancer cells resulted in a novel inhibition of ER-mediated gene expression and cell proliferation/ survival.
Glyceollin I may represent an important component of a phytoalexin-enriched food (activated) diet in terms of chemoprevention as well as a novel therapeutic (Tilghman et al., 2010).
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