Quercetin, a flavonoid found in foods like onions, apples, and tea, has shown promise in prostate cancer research due to its anti-inflammatory, antioxidant, and anticancer properties. Here’s a concise overview based on available evidence:
Mechanisms of Action:
- Apoptosis and Cell Cycle Arrest: Quercetin induces programmed cell death (apoptosis) in prostate cancer cells (e.g., LNCaP, PC-3, DU-145) by modulating pathways like PI3K/Akt, NF-κB, and ROS, while sparing normal prostate cells. It arrests the cell cycle, often at G1 or G2/M phases, reducing cancer cell proliferation.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001031/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036441/
- Androgen Receptor (AR) Inhibition: Quercetin downregulates AR expression and function, reducing prostate-specific antigen (PSA) and other androgen-regulated markers, critical in both androgen-sensitive and castration-resistant prostate cancer (CRPC).https://academic.oup.com/carcin/article-abstract/22/3/409/2733786?redirectedFrom=fulltext
- Anti-Metastatic Effects: It suppresses epithelial-to-mesenchymal transition (EMT) by inhibiting TGF-β signaling, reducing metastasis in aggressive cell lines like PC-3.https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1077531/full
- Angiogenesis Inhibition: Quercetin inhibits vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1), limiting tumor blood supply.https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1077531/fullhttps://pubmed.ncbi.nlm.nih.gov/37232542/
- Chemosensitization: Quercetin enhances the efficacy of drugs like docetaxel and reverses chemoresistance (e.g., doxorubicin resistance) by targeting PI3K/Akt pathways, potentially reducing required doses and toxicity.https://www.mdpi.com/2072-6694/15/3/902https://pmc.ncbi.nlm.nih.gov/articles/PMC8036441/
In Vitro and In Vivo Evidence:
- Cell Lines: Studies show quercetin inhibits proliferation and induces apoptosis in androgen-sensitive (LNCaP) and androgen-independent (PC-3, DU-145) prostate cancer cells, with IC50 values around 22–23 µM.https://www.researchgate.net/publication/274642963_Quercetin_in_prostate_cancer_Chemotherapeutic_and_chemopreventive_effects_mechanisms_and_clinical_application_potential_Review
- Animal Models: In rats induced with prostate cancer (MNU and testosterone), quercetin (200 mg/kg) reduced tumor growth by downregulating IGF-1/IGF-1R, Akt, and AR, while boosting antioxidant enzymes and apoptotic proteins.https://pubmed.ncbi.nlm.nih.gov/24080313/
- Epidemiology: Higher dietary quercetin intake correlates with a reduced prostate cancer risk, with one study showing a 50% lower risk in men with the highest intake.https://www.tandfonline.com/doi/full/10.2144/fsoa-2023-0041
Clinical Considerations:
- Bioavailability: Quercetin’s low bioavailability limits its clinical use. Nano-delivery systems (e.g., PLGA nanoparticles, micelles) improve tumor targeting and efficacy.https://pmc.ncbi.nlm.nih.gov/articles/PMC8036441/
- Combination Therapy: Quercetin synergizes with TRAIL or docetaxel, enhancing apoptosis and overcoming resistance, suggesting potential as an adjunct therapy.https://pubmed.ncbi.nlm.nih.gov/34311541/https://www.mdpi.com/2072-6694/15/3/902
- Double-Edged Sword: In early-stage, androgen-dependent cancers (LNCaP), quercetin may upregulate VEGF-c, potentially promoting progression, but it reduces VEGF-a in advanced, androgen-independent cases (PC-3), indicating stage-specific effects.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273064/
Limitations and Future Directions:
- Clinical trials are scarce, with limited human data on efficacy and optimal dosing. Pharmacokinetic studies show promise but need validation.https://pubmed.ncbi.nlm.nih.gov/25845380/
- Quercetin’s effects on cancer stem cells and long-term outcomes require further exploration.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273064/
- Its role in modulating OPN and VEGF isoforms suggests a need for personalized approaches based on cancer stage and androgen status.https://pubmed.ncbi.nlm.nih.gov/37232542/
Conclusion: Quercetin exhibits significant anti-prostate cancer effects through multiple mechanisms, particularly in advanced or resistant cases, and holds potential as a chemopreventive or adjunct therapy. However, its stage-specific effects and bioavailability challenges necessitate further research, especially clinical trials, to optimize its therapeutic application. Always consult a healthcare provider before considering quercetin supplementation, as it may interact with medications or affect cancer progression variably.
