title: Prostatic fluid concentrations of isoflavonoids in soy consumers are sufficient to inhibit growth of benign and malignant prostatic epithelial cells in vitro.
abstract: BACKGROUND
  The differential intestinal metabolism of the soy isoflavones is likely to influence the ability of soy to prevent prostate cancer. While daidzein, genistein, and equol have direct antiproliferative effects on prostatic epithelial cells in vitro, there are no such data for the isoflavone glycitein, or seven metabolites: O-desmethylangolensin (ODMA), 6-hydroxyODMA (6H-ODMA), dihydrodaidzein (DHD), cis-4-hydroxyequol (C4HE), 3'-hydroxydaidzein (3HD), 6-hydroxydaidzein (6HD), and 8-hydroxydaidzein (8HD). In the current study, the in vitro activities of these compounds were elucidated, and the active ranges of concentrations were compared to that found in Caucasian prostatic fluid (PF) and plasma samples.
  
  
  METHODS
  The effects of isoflavonoids on cell growth, cell cycle distribution, and apoptosis (active Caspase 3) were examined on benign prostatic epithelial cells (PrEC), and the prostate cancer cell line LNCaP.
  
  
  RESULTS
  PF concentrations of genistein, equol, and daidzein (but not ODMA or DHD) were often within the ranges that reduce PrEC growth in vitro. Profound differences in sensitivities were observed with LNCaP. The hydroxydaidzeins, C4HE, and 6H-ODMA had significant inhibitory effects at 10(-5)M on PrEC growth (but not LNCaP). Glycitein had significant effects on both. Reductions in cell growth were typically associated with both changes in cell cycle distribution and Caspase 3 activation. When five isoflavonoids were used in combination at concentrations present in PF samples, synergistic effects were observed.
  
  
  CONCLUSIONS
  The profound differences in sensitivities of prostatic epithelial cells to these compounds along with their synergistic effects suggest that multiple metabolites in vivo may be optimal for preventing prostate cancer.
authors.affiliation: Department of Pathology, The University of Colorado at Denver and Health Sciences Center, School of Medicine, Aurora, USA. tammy.hedlund@UCHSC.edu
authors.forename: Tammy E
authors.initials: TE
authors.lastname: Hedlund
authors.forename: Adrie
authors.initials: A
authors.lastname: van Bokhoven
authors.forename: Widya U
authors.initials: WU
authors.lastname: Johannes
authors.forename: Steven K
authors.initials: SK
authors.lastname: Nordeen
authors.forename: Lorraine G
authors.initials: LG
authors.lastname: Ogden
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004032:Diet; D006801:Humans; D007529:Isoflavones / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D030262:Soybean Proteins
chemical_list: D007529:Isoflavones; D030262:Soybean Proteins