TY - JOUR
T1 - Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy
AU - Zimmermann, M. Carla
AU - Tilghman, Syreeta L.
AU - Boué, Stephen M.
AU - Salvo, Virgilio A.
AU - Elliott, Steven
AU - Williams, K. Y.
AU - Skripnikova, Elena V.
AU - Ashe, Hasina
AU - Payton-Stewart, Florastina
AU - Vanhoy-Rhodes, Lyndsay
AU - Fonseca, Juan Pablo
AU - Corbitt, Cynthia
AU - Collins-Burow, Bridgette M.
AU - Howell, Melanie H.
AU - Lacey, Michelle
AU - Shih, Betty Y.
AU - Carter-Wientjes, Carol
AU - Cleveland, Thomas E.
AU - McLachlan, John A.
AU - Wiese, Thomas E.
AU - Beckman, Barbara S.
AU - Burow, Matthew E.
PY - 2010/1
Y1 - 2010/1
N2 - Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen. By isolating the individual glyceollin isomers (I, II, and III), we have identified the active antiestrogenic component by using competition binding assays with human ERα and in an estrogen-responsive element-based luciferase reporter assay. We identified glyceollin I as the active component of the combined glyceollin mixture. Ligand-receptor modeling (docking) of glyceollin I, II, and III within the ERα ligand binding cavity demonstrates a unique type II antiestrogenic confirmation adopted by glyceollin I but not isomers II and III. We further compared the effects of glyceollin I to the antiestrogens, 4-hydroxytamoxifen and ICI 182,780 (fulvestrant), in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on 17β-estradiol- stimulated expression of progesterone receptor and stromal derived factor-1α. Our results establish 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 agent for hormone-dependent tumors.
AB - Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen. By isolating the individual glyceollin isomers (I, II, and III), we have identified the active antiestrogenic component by using competition binding assays with human ERα and in an estrogen-responsive element-based luciferase reporter assay. We identified glyceollin I as the active component of the combined glyceollin mixture. Ligand-receptor modeling (docking) of glyceollin I, II, and III within the ERα ligand binding cavity demonstrates a unique type II antiestrogenic confirmation adopted by glyceollin I but not isomers II and III. We further compared the effects of glyceollin I to the antiestrogens, 4-hydroxytamoxifen and ICI 182,780 (fulvestrant), in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on 17β-estradiol- stimulated expression of progesterone receptor and stromal derived factor-1α. Our results establish 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 agent for hormone-dependent tumors.
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U2 - 10.1124/jpet.109.160382
DO - 10.1124/jpet.109.160382
M3 - Article
C2 - 19797619
AN - SCOPUS:73949159503
SN - 0022-3565
VL - 332
SP - 35
EP - 45
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -