Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608066
Poster Session
Georg Thieme Verlag KG Stuttgart · New York

Urolithins, gut microbiota metabolites of ellagitannins, in prostate cancer chemoprevention.

I Stanisławska
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
,
J Piwowarski
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
,
S Granica
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
,
A Kiss
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 
 

    Urolithins are well bioavailable products of ellagitannin degradation by gut microbiota. These compounds have numerous biological activities, including anti-cancer [1].

    In this study, we focused on the effects of urolithins on androgen receptor activity, which is crucial in prostate cancer development and progression.

    We incubated androgen-dependent LNCaP cells with urolithins A, B and C (5 – 50µM, 72h) and their mixtures with 10µM bicalutamide, a clinically used non-steroidal antiandrogen. Cell proliferation was determined by measurement of DNA-Hoechst 33258 complexes fluorescence in cells lysates. Apoptosis was detected by flow cytometry after annexin V-FITC and PI staining. PSA secretion was measured with PSA total ELISA kit. Androgen receptor localization was examined by flow cytometry. Urolithin A and B showed similar anti-proliferative activity with IC50= 32.6 ± 2.7µM and IC50= 35.7 ± 0.9µM, respectively, while urolithin C had slightly weaker effect (IC50= 45.5 ± 3.7µM). Bicalutamide had additive anti-proliferative effect with urolithin A (CI = 0.86 ± 0.08) and B (CI = 1.06 ± 0.08) and antagonistic with urolithin C (CI = 2.27 ± 0.95). Urolithins induced apoptosis of LNCaP cells. Urolithin A was the most and urolithin C the least active metabolite (40µM, 25.7 ± 0.9% and 16,13 ± 1.0% of apoptotic cells, p < 0.05 respectively). Bicalutamide attenuated apoptosis induced by urolithin A and B. Urolithin A and urolithin C decreased dihydrotestosterone-stimulated PSA secretion to 56.9 ± 3.3% and 81.0 ± 5.6%, respectively. Urolithin B counteracted bicalutamide-induced decrease in PSA secretion (p < 0.05). Moreover, urolithin A promoted cytoplasmic localization of androgen receptor irrelevant of the presence of bicalutamide. Our results show that urolithins may contribute to chemopreventive activity of ellagitannin rich preparations. However, observed interactions with clinically used drug warrant further study to determine safety of ellagitannin supplementation during hormonal therapy of prostate cancer.

    [1] Espin JC, Larrosa M, Garcia-Conesa MT, Tomas-Barberan F. Evid Based Complement Alternat Med 2013; 2013: Article Number 270418


    #