title: Impact of lower concentrations of phytoestrogens on the effects of estradiol in breast cancer cells.
abstract: OBJECTIVE
  To explore the impact of lower concentrations of phytoestrogens on 17β-estradiol (E2) in the growth of MCF-7 breast cells.
  
  
  METHODS
  MCF-7 cells were treated with E2 (10(-8) mol/l), one of three phytoestrogens (genistein, resveratrol, and quercetin) (10(-7)  to 10(-5) mol/l), and with a combination of both E2 and one of these phytoestrogens for 48 h. These cells were then extracted for MTT and TUNEL assay. Western blot was utilized to evaluate the proteins involved in the proliferative and apoptotic pathways, as well as the differential effects on ERα and β.
  
  
  RESULTS
  MCF-7 cell proliferations were induced by both E2 alone and E2 plus one of the three phytoestrogens (at concentrations ≥ 10(-6) mol/l). Apoptotic cells were significantly increased in the phytoestrogen-treated MCF-7 cells and, conversely, suppressed in the cells treated with both E2 and phytoestrogens. Proliferating cell nuclear antigen, PI3K and p-Akt were increased in the cultures with E2 and substantially more in the cultures with E2 plus a phytoestrogen. The combination of E2 and phytoestrogen significantly inhibited the increase in FADD, cytochrome C, truncated Bid, caspase-9, caspase-3 and ERβ that was induced by phytoestrogens in the MCF-7. ERα expression was significantly induced by E2 regardless of the presence of these phytoestrogens.
  
  
  CONCLUSIONS
  This study demonstrates that, in the presence of E2, genistein, resveratrol, and quercetin may stimulate breast cancer cells, even at low physiological concentrations. Therefore, the conflicting results regarding the effects of phytoestrogens on breast cells may be attributed to the endogenous estrogen present in breast tissue.
authors.affiliation: Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung and Chang Gung University , Taiwan.
authors.forename: F-P
authors.initials: FP
authors.lastname: Chen
authors.forename: M-H
authors.initials: MH
authors.lastname: Chien
authors.forename: I Y-Y
authors.initials: IY
authors.lastname: Chern
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D061986:MCF-7 Cells; D048789:Phytoestrogens / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D048789:Phytoestrogens; D013267:Stilbenes; D004958:Estradiol; D011794:Quercetin; D019833:Genistein; D000077185:Resveratrol
keywords: 17β-ESTRADIOL; GENISTEIN; MCF-7 BREAST CANCER CELLS; PHYTOESTROGENS; QUERCETIN; RESVERATROL