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Updated: May 2, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo
Dong-Sheng Ming1, Steven Pham1, Subrata Deb1
1Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Castration-resistant prostate cancer (CRPC) remains largely dependent on androgen receptor (AR). Residual tissue androgens are consistently detected within CRPC tumors and play a critical role in facilitating AR-mediated signaling pathways which lead to disease progression. Testosterone and dihydrotestosterone (DHT) are the major androgens detected in tumors. They are produced through three biosynthesis pathways: Δ(4), Δ(5), and backdoor pathways. Both androgens bind to and stimulate AR activation. The current study investigates the effects of pomegranate extracts (POM) and their ability to inhibit androgen biosynthesis using PCa cell lines (22RV1 and LNCaP) in vitro as well as the PTEN knockout mouse model representing prostate cancer. Steroids were extracted using ethyl acetate or solid phase extraction, and then analyzed by UPLC/MS/MS. The results showed that POM (0-12μg/mL) reduced the production of testosterone, DHT, DHEA, androstenedione, androsterone, and pregnenolone in both cell lines. In addition our in vivo data supports this observation with a reduction in serum steroids determined after 20 weeks of POM treatment (0.17 g/L in drinking water). In accordance with these results, Western blotting of cell lysates and tPSA analysis determined that PSA was significantly decreased by the treatment of POM. Interestingly, AKR1C3 and AR levels were shown to be increased in both cell lines, perhaps as a negative feedback effect in response to steroid inhibition. Overall, these results provide mechanistic evidence to support the rationale for recent clinical reports describing efficacy of POM in CRPC patients.
Insights
Pomegranate extracts (POM) reduce key androgen production in prostate cancer cells and mouse models. This suggests POM may be a viable therapeutic strategy for castration-resistant prostate cancer (CRPC) by inhibiting androgen receptor signaling.
Area of Science:
- Oncology
- Endocrinology
- Biochemistry
Background:
- Castration-resistant prostate cancer (CRPC) progression is driven by androgen receptor (AR) signaling, fueled by residual androgens like testosterone and dihydrotestosterone (DHT).
- Androgen biosynthesis occurs via multiple pathways, and these androgens remain critical for AR activation and disease advancement in CRPC.
Purpose of the Study:
- To investigate the efficacy of pomegranate extracts (POM) in inhibiting androgen biosynthesis pathways.
- To evaluate the impact of POM on prostate cancer cell lines and a preclinical prostate cancer mouse model.
Main Methods:
- In vitro studies utilized PCa cell lines (22RV1 and LNCaP) treated with POM.
- Steroid analysis was performed using UPLC/MS/MS after ethyl acetate or solid phase extraction.
- In vivo efficacy was assessed in a PTEN knockout mouse model treated with POM in drinking water.
- Western blotting and tPSA analysis were used to measure protein and PSA levels.
Main Results:
- POM treatment significantly reduced the production of testosterone, DHT, DHEA, androstenedione, androsterone, and pregnenolone in both cell lines.
- In vivo studies confirmed a reduction in serum steroids after 20 weeks of POM administration.
- POM treatment led to a significant decrease in prostate-specific antigen (PSA) levels.
- AKR1C3 and AR levels increased in response to POM, suggesting a potential negative feedback mechanism.
Conclusions:
- Pomegranate extracts effectively inhibit androgen biosynthesis and reduce PSA levels in preclinical models of prostate cancer.
- The findings provide mechanistic support for the clinical observation of POM efficacy in CRPC patients.
- POM represents a potential therapeutic agent targeting AR signaling in CRPC.
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