title: Physiological concentrations of genistein and 17β-estradiol inhibit MDA-MB-231 breast cancer cell growth by increasing BAX/BCL-2 and reducing pERK1/2.
abstract: OBJECTIVE
  The aim of the present study was to identify the mechanism by which genistein and 17β-estradiol inhibit proliferation of MDA-MB-231 breast cancer cells.
  
  
  METHODS
  The expression of cell signaling proteins involved in cell apoptosis, proliferation, and survival (BCL-2 associated X protein, BAX; B-cell lymphoma 2, BCL-2; extracellular signal regulated kinase, pERK1/2; and protein kinase B, pAKT) were examined by western blotting, and tested whether these effects correlated with cell proliferation and apoptosis.
  
  
  RESULTS
  Compared to the control, 1 μM genistein plus 1 nM 17β-estradiol significantly increased apoptosis, and the BAX/BCL-2 ratio, with a concomitant decrease in ERK1/2 phosphorylation. High concentrations of genistein (100 μM) both in the presence and absence of 17β-estradiol also increased apoptosis; however, these changes were not correlated with the BAX/BCL-2 ratio or with phosphorylation of ERK1/2.
  
  
  CONCLUSIONS
  These results suggest that different concentrations of genistein elicit cell responses through different signaling mechanisms. These results are especially relevant in premenopausal women with breast cancer who are on a soy diet.
authors.affiliation: Department of Biological Sciences, DePaul University, Chicago, IL 60614, USA. trajah@depaul.edu
authors.forename: Talitha T
authors.initials: TT
authors.lastname: Rajah
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Peine
authors.forename: Nga
authors.initials: N
authors.lastname: Du
authors.forename: Christina A
authors.initials: CA
authors.lastname: Serret
authors.forename: Neil R
authors.initials: NR
authors.lastname: Drews
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051028:bcl-2-Associated X Protein; D004958:Estradiol; D019833:Genistein; D048049:Extracellular Signal-Regulated MAP Kinases