Ericifolin: A novel antitumor compound from allspice that silences androgen receptor in prostate cancer

Nagarajarao Shamaladevi, Dominic A. Lyn, Khaled A. Shaaban, Lei Zhang, Susana Villate, Jürgen Rohr, Bal L. Lokeshwar

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1822-1832
Number of pages11
JournalCarcinogenesis
Volume34
Issue number8
DOIs
StatePublished - Aug 1 2013

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Shamaladevi, N., Lyn, D. A., Shaaban, K. A., Zhang, L., Villate, S., Rohr, J., & Lokeshwar, B. L. (2013). Ericifolin: A novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis, 34(8), 1822-1832. https://doi.org/10.1093/carcin/bgt123