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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by
Lunyin Yu1, George L Blackburn, Jin-Rong Zhou
1Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Abstract:
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.
Insights
Soy isoflavones like genistein and daidzein can inhibit prostate cancer growth by reducing the expression of the androgen-regulated PART-1 gene. This suggests a potential dietary strategy for prostate cancer prevention.
Area of Science:
- Oncology
- Nutritional Science
- Molecular Biology
Background:
- Epidemiologic and laboratory studies suggest soy phytochemicals may prevent prostate cancer.
- Identifying genes sensitive to androgen regulation and prostate cancer prevention is a research priority.
Purpose of the Study:
- To determine the effect of soy isoflavones on the expression of prostate androgen-regulated transcript 1 (PART-1).
- To investigate PART-1 as a potential novel androgen-dependent prostate cancer tumor marker.
Main Methods:
- Utilized an androgen-depleted cell culture system with LNCaP, DU 145, and PC-3 human prostate cancer cells.
- Administered 5alpha-dihydrotestosterone (DHT) to induce PART-1 expression.
- Treated cells with soy isoflavones (genistein, daidzein, glycitein) to assess their inhibitory effects on DHT-induced PART-1 expression.
Main Results:
- DHT induced PART-1 transcript expression in androgen-sensitive LNCaP cells, but not in androgen-independent DU 145 or PC-3 cells.
- Genistein and daidzein dose-dependently inhibited DHT-induced PART-1 expression in LNCaP cells.
- Genistein demonstrated significant inhibition, while daidzein was less potent, and glycitein showed no inhibitory effect.
Conclusions:
- Soy isoflavones, particularly genistein, can inhibit the expression of the androgen-induced PART-1 gene in prostate cancer cells.
- The PART-1 gene may serve as a biomarker for evaluating the efficacy of soy isoflavones in managing androgen-dependent prostate cancer.
- Further investigation is warranted to explore PART-1's role in soy-based prostate cancer prevention strategies.

