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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Urolithins: Emerging natural compound targeting castration-resistant prostate cancer (CRPC)
Ajit Kumar Navin1, Chalikkaran Thilakan Rejani2, Balaji Chandrasekaran1
1Department of Pharmacology, College of Pharmacy, Texas A&M University, College Station, TX 77845, USA.
Abstract:
Castration-resistant prostate cancer (CRPC) presents a significant challenge due to its resistance to conventional androgen deprivation therapies. Urolithins, bioactive metabolites derived from ellagitannins, have recently emerged as promising therapeutic agents for CRPC. Urolithins not only inhibit androgen receptor (AR) signaling, a crucial factor in the progression of CRPC, but also play a key role in regulating oxidative stress by their antioxidant properties, thereby inhibiting increased reactive oxygen species, a common feature of the aggressive nature of CRPC. Research has shown that urolithins induce apoptosis and diminish pro-survival signaling, leading to tumor inhibition. This review delves into the intricate mechanisms through which urolithins exert their therapeutic effects, focusing on both AR-dependent and AR-independent pathways. It also explores the exciting potential of combining urolithins with androgen ablation therapy, opening new avenues for CRPC treatment.
Insights
Urolithins show promise in treating castration-resistant prostate cancer (CRPC) by inhibiting androgen receptor signaling and reducing oxidative stress. These compounds may offer new therapeutic strategies, potentially combined with existing treatments.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Castration-resistant prostate cancer (CRPC) is a major clinical challenge due to therapy resistance.
- Androgen receptor (AR) signaling drives CRPC progression.
- Oxidative stress contributes to CRPC aggressiveness.
Purpose of the Study:
- To review the therapeutic potential of urolithins for CRPC.
- To elucidate the mechanisms of urolithin action in CRPC.
- To explore combination therapies involving urolithins.
Main Methods:
- Literature review of preclinical and clinical studies on urolithins and CRPC.
- Analysis of AR-dependent and AR-independent signaling pathways.
- Evaluation of antioxidant and pro-apoptotic effects of urolithins.
Main Results:
- Urolithins inhibit AR signaling and exhibit antioxidant properties.
- Urolithins induce apoptosis and suppress pro-survival pathways in CRPC cells.
- Urolithins demonstrate tumor inhibitory effects.
Conclusions:
- Urolithins represent a promising therapeutic class for CRPC.
- Their mechanisms involve both AR-dependent and independent pathways.
- Combination therapy with androgen ablation warrants further investigation.
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