The main goal of this project is to develop a chemo-dietary prevention strategy against prostate cancer using a novel compound from the aromatic berries of a Jamaican plant (Pimenta dioica), known as Allspice, a common spice in all cuisines. The new compound, Ericifolin (EF), a polyphenol, was isolated from the Aqueous Allspice Extract (AAE). Preliminary studies using the AAE showed strong and specific activity against prostate cancer cell proliferation and induced multiple anti-tumor activities including apoptosis, cell cycle arrest, and repression of androgen receptor transcription and tumor growth inhibition. The purified Ericifolin showed key biological functions of AAE in cell culture studies. The project is to perform a comprehensive investigation of the anticancer activities of EF on preclinical models of prostate cancer to establish the translational potential of EF for human consumption as a cancer chemo-preventive agent. Hypotheses: 1. EF will control prostate cancer growth and progression in orthotopic and and transgenic models of prostate cancer, with minimal systemic toxicity. 2. The antitumor effects of EF are due to the down regulation of androgen receptor and AKT and their down-stream pro-survival signals.
Specific Aims : 1. Investigate in vivo efficacy of EF and AAE in orthotopic and xenografts of prostate cancer cells (LNCaP, LAPC-4 and PC-3). 2: Establish the mechanism of antitumor action of EF using molecular, cellular and genetic approaches in both androgen-dependent and castration resistant prostate cancer cells;3. Investigate the stage-specific chemo preventive effects of EF in the Prostate-PTEN knockout transgenic model to determine the dose and stage-specific efficacy. Systemic toxicity, pharmacokinetics of EF will be established for further clinical testing in patients. This is the first investigation of a new, potentially effective anticancer agent, EF. Evaluation of the efficacy in pre-clinical models, bioavailability, and toxicity should allow designing of phase I clinical trials for prostate cancer, at the end of this investigation.

Public Health Relevance

This project is to investigate the chemopreventive and therapeutic efficacy of Ericifolin, a natural polyphenol from aqueous extract of Allspice berries against prostate cancer. Evaluation of its efficacy in pre-clinical models of prostate cancer and determining bioavailability, potential systemic toxicity and clearance from plasma should allow further development of Ericifolin for clinical applications.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA156776-04
Application #
8625718
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Perloff, Marjorie
Project Start
2011-01-01
Project End
2016-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
4
Fiscal Year
2014
Total Cost
$290,041
Indirect Cost
$100,472
Name
University of Miami School of Medicine
Department
Urology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
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Shamaladevi, Nagarajarao; Lyn, Dominic A; Shaaban, Khaled A et al. (2013) Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis 34:1822-32
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