Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro.
BACKGROUND
The dietary consumption of high levels of soy has been linked to reduced risks for prostate cancer (PC) in Asians and vegetarians. In vitro studies have focused on the two most abundant isoflavones in soy, genistein and daidzein. However, daidzein is differentially metabolized by gut microflora in humans, yielding compounds with very different bioactivities and half-lives. Asians are significantly more likely to produce the metabolite equol than Caucasians, suggesting its role in the prevention of PC. We hypothesize that equol is a bioactive metabolite that exerts direct antiproliferative effects on prostatic epithelial cells.


METHODS
Benign and malignant prostatic epithelial cells were treated in vitro with equol, genistein, and daidzein by using the range of concentrations found in the prostatic fluids of Asians consuming soy. Growth and cell cycle distribution were analyzed over time.


RESULTS
After 9 days of treatment, equol inhibited growth of benign human prostatic epithelial cells (PrEC) by 37% at 10(-6) M and 80% at 10(-5) M. Although genistein also had profound effects, daidzein appeared only one tenth as potent as equol. Equol and daidzein caused an accumulation of cells in G0/G1, whereas genistein arrested cells in G2/M. The isoflavonoids demonstrated differential effects on the established PC cell lines 22Rv1, LNCaP, LAPC-4, PC-3, and DU 145. PC-3 cells showed the greatest resistance.


CONCLUSIONS
Equol is a biologically active metabolite of daidzein that has potent antiproliferative effects on benign and malignant prostatic epithelial cells at concentrations that can be obtained naturally through dietary soy consumption.
Hedlund
Tammy E
TE
University of Colorado Health Sciences Center, Department of Pathology, Denver, Colorado 80262, USA. tammy.hedlund@uchsc.edu
Johannes
Widya U
WU
Miller
Gary J
GJ
D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D060754:Equol; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D010940:Plant Proteins; D011134:Polysaccharides; D011467:Prostate / Q000166:cytology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D045730:Soy Foods; D014407:Tumor Cells, Cultured
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D002839:Chromans; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D010940:Plant Proteins; D011134:Polysaccharides; C412882:okara, Glycine max; D060754:Equol; C004742:daidzein; D019833:Genistein