Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596836
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

5-(3',4',5'-trihydroxyphenyl)-γ-valerolactone and nasutin A inhibit LNCaP prostate cancer cell proliferation

IJ Stanisławska
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1 St., 02 – 097 Warsaw, Poland
,
S Granica
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1 St., 02 – 097 Warsaw, Poland
,
JP Piwowarski
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1 St., 02 – 097 Warsaw, Poland
,
J Szawkało
2   Laboratory of Natural Products Chemistry, University of Warsaw, Pasteura 1 St., 02 – 093 Warsaw, Poland
,
K Wiązecki
2   Laboratory of Natural Products Chemistry, University of Warsaw, Pasteura 1 St., 02 – 093 Warsaw, Poland
,
Z Czarnocki
2   Laboratory of Natural Products Chemistry, University of Warsaw, Pasteura 1 St., 02 – 093 Warsaw, Poland
,
AK Kiss
1   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1 St., 02 – 097 Warsaw, Poland
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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Complementary and alternative medicine (CAM) is popular among prostate cancer patients. Herbal preparations, such as green tea and pomegranate extracts, are one of the most commonly used forms of CAM [1]. Whole extracts and their main chemical constituents are used during studies of herbal preparations efficacy. However, flavan-3-ols and ellagitannins undergo extensive metabolism by gut microbiota, which yields bioavailable compounds [2, 3]. Here, we examined the effects of 5-(3',4',5'-trihydroxyphenyl)-γ-valerolactone (M4 VL) and nasutin A (concentration 1 – 100µM; 24 – 72h) on LNCaP prostate cancer cells proliferation and interaction between M4 VL and urolithin A, common ellagitannin metabolite in humans. M4 VL, epigallocatechin gallate (EGCG) ring fission metabolite, and nasutin A, ellagitannin metabolite produced in mammals, were synthetized. Their purity and structures were confirmed by HPLC-DAD-MS and NMR methods. Cell proliferation was determined by measurement of DNA-Hoechst 33258 complexes fluorescence intensity in cell lysates. Interaction studies were performed using Chou and Talalay combination index (CI) method4. M4 VL and nasutin A dose and time-dependently inhibited LNCaP cells proliferation (p < 0,05). The IC50 of nasutin A was 55.2 ± 2.0µM after 24h and decreased to 30.7 ± 2.7µM after 72h of incubation. M4 VL (100µM) inhibited 28.3 ± 6.0% and 46.0 ± 3.9% of cell proliferation after 24h and 72h, respectively. Combination of M4 VL and urolithin A had additive antiproliferative effect on LNCaP cells (CI = 1.05 ± 0.06). These results suggest that gut metabolites may contribute to the effects observed after ingestion of flavan-3-ols and ellagitannins and add rationale to their application as CAM in prostate cancer.

Keywords: Flavan-3-ol metabolite, 5-(3',4',5'-trihydroxyphenyl)-γ-valerolactone, ellagitannin metabolite, nasutin A, prostate cancer.

References:

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