Mechanisms of anti-proliferative effects of glyceollins in estrogen-dependent and -independent tumor cells
Description
Glyceollin, a phytoestrogen isolated from soy, has recently been demonstrated to be an anti-estrogen with respect to estrogen receptor (ER), and an inhibitor of 17beta-estradiol-induced tumor progression. This novel project will be focused on the mechanisms of action of the phytoalexin glyceollin I Here, we investigated for the first time the antiestrogenic activities of glyceollin isomers (I, II and III) in a competition binding assay with human estrogen receptor alpha (hrER-alpha) and in an estrogen response element luciferase assay (ERE-Luc). We were able to identify the isomer glyceollin I as the active component of the mix. We also report studies evaluating the effects of glyceollin I in comparison to 4-hydroxy-tamoxifen (4-OH-Tam), ICI 182,780, and 17beta-estradiol (E2) in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on the expression patterns of two genes: progesterone receptor (PgR) and stromal derived factor-1alpha (SDF-1alpha). In addition, the influence of this compound on cell proliferation and viability utilizing a well established clonogenic assay method was assessed. Furthermore, inhibition of proliferation on MDA-MB 231 ER-negative breast cancer cells was demonstrated. Taken together, our results support the hypothesis of a novel in vitro inhibition of estrogen-dependent and estrogen-independent cell proliferation. Although further studies will be needed, glyceollin I may represent an important component of a soy-based diet in terms of chemoprevention and treatment of estrogen-related cancer