Prostatic fluid concentrations of isoflavonoids in soy consumers are sufficient to inhibit growth of benign and malignant prostatic epithelial cells in vitro

• Published in: The Prostate 2006-04, Vol.66 (5), p.557-566
• Main Authors: Hedlund, Tammy E., Bokhoven, Adrie van, Johannes, Widya U., Nordeen, Steven K., Ogden, Lorraine G.
• Format: Article
• Language: English
• Subjects: apoptosis; Biological and medical sciences; Cell Division - drug effects; Cell Line, Tumor; cis-4 hydroxyequol; daidzein; Diet; dihydrodaidzein; equol; Gynecology. Andrology. Obstetrics; Humans; hydroxydaidzein; hydroxyodma; Isoflavones - isolation & purification; Isoflavones - metabolism; Isoflavones - pharmacology; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; O-desmethylangolensin; Prostate - cytology; Prostate - drug effects; Prostate - metabolism; prostate cancer prevention; Prostatic Neoplasms - pathology; Soybean Proteins; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20380

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 10−5M 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. CONCLUSION 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. Prostate © 2005 Wiley‐Liss, Inc.