Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells.
Epidemiologic investigations and laboratory studies suggest that bioactive soy phytochemical components may be used as an effective dietary regimen for prevention of prostate cancer. Studies designed to identify new genes that are responsive to androgens and are sensitive to the prevention of prostate cancer using soy bioactive components have become a research priority. In this study, we determined the effect of soy isoflavones on the expression of prostate androgen-regulated transcript 1 (PART-1), a newly discovered androgen-induced gene that may represent a novel androgen-dependent prostate cancer tumor marker. In an androgen-depleted cell culture system, 5alpha-dihydrotestosterone (DHT) induced expression of PART-1 transcript in androgen-sensitive LNCaP, but not in androgen-independent DU 145 or PC-3 human prostate cancer cells. The soy isoflavones genistein and daidzein dose-dependently inhibited DHT-induced expression of the PART-1 transcript. Genistein at 50 micro mol/L completely inhibited expression of the PART-1 transcript in LNCaP cells induced by DHT at 0.1 and 1.0 nmol/L. Daidzein was less potent than genistein, whereas glycitein at the same levels as genistein or daidzein did not inhibit DHT-induced PART-1 transcript expression. Our studies suggest that use of the PART-1 gene as a biomarker for evaluating the efficacy of soy isoflavones on androgen-dependent prostate cancer warrants further investigation.
Yu
Lunyin
L
Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Blackburn
George L
GL
Zhou
Jin-Rong
JR
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000627:therapeutic use*; D006801:Humans; D007529:Isoflavones / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects* / Q000235:genetics; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; C407989:JTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D013196:Dihydrotestosterone; C004742:daidzein; D019833:Genistein