Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer
| Autor: | Dominic A. Lyn, Balakrishna L. Lokeshwar, Lei Zhang, Khaled A. Shaaban, Jürgen Rohr, Susana Villate, Nagarajarao Shamaladevi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Pimenta Cancer Research Programmed cell death Transcription Genetic Mice Nude Antineoplastic Agents Apoptosis Original Manuscript Biology Cell Line S Phase Mice Random Allocation chemistry.chemical_compound DU145 Cell Line Tumor Eugenol LNCaP Autophagy Animals Humans Gene Silencing Glycosides RNA Messenger Promoter Regions Genetic Cell Proliferation Cell growth Cell Cycle G1 Phase General Medicine Fibroblasts Cell cycle Xenograft Model Antitumor Assays Molecular biology Androgen receptor Prostatic Neoplasms Castration-Resistant chemistry Receptors Androgen Caspases Poly(ADP-ribose) Polymerases Growth inhibition |
| Zdroj: | Carcinogenesis. 34:1822-1832 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgt123 |
| Popis: | Silencing of androgen receptor (AR) signaling is a specific and effective mechanism to cure cancer of the prostate (CaP). In this study, the isolation and characterization of a compound from the aromatic berries of Pimenta dioica (allspice) that silences AR is presented. Potential antitumor activities of an aqueous allspice extract (AAE) and a compound purified from the extract were tested on CaP cells. AAE inhibited tumor cell proliferation and colony formation (50% growth inhibition ∼40–85 µg/ml) but not the viability of quiescent normal fibroblasts or non-tumorigenic prostate cells. In tumor cells, AAE inhibited cell cycle progression at G1/S, induced apoptosis or autophagy. Apoptosis was by caspase-dependent poly (ADP ribose) polymerase cleavage. A caspase-independent, apoptosis-inducing factor-mediated mechanism of apoptosis caused cell death in castration-resistant AR-positive or AR-negative CaP cells, such as CWR22RV1, PC-3 or DU145 cells. Treatment with AAE decreased the levels of AR messenger RNA (mRNA), protein and silenced AR activity in AR-positive cells. AR depletion was due to inhibition of AR promoter activity and mRNA stability. Delayed tumor growth (~55%) without measurable systemic toxicity was observed in LNCaP tumor-bearing mice treated with AAE by oral or intraperitoneal routes. LNCaP tumor tissues from AAE-treated mice revealed increased apoptosis as a potential mechanism of antitumor activity of AAE. The chemical identity of bioactive compound in AAE was established through multistep high-performance liquid chromatography fractionation, mass and Nuclear Magnetic Resonance spectroscopies. The compound, eugenol 5-O-β-(6′-galloylglucopyranoside) or ericifolin (EF), showed antiproliferative, pro-apoptosis and anti-AR transcription activities. These results demonstrate a potential use of AAE and EF against prostate cancer. |
| Databáze: | OpenAIRE |
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