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.
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.
|Hoy, James J; Kallifatidis, Georgios; Smith, Diandra K et al. (2017) Inhibition of androgen receptor promotes CXC-chemokine receptor 7-mediated prostate cancer cell survival. Sci Rep 7:3058|
|Kallifatidis, Georgios; Munoz, Daniel; Singh, Rajendra Kumar et al. (2016) ?-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation. Mol Cancer Res 14:493-503|
|Kallifatidis, Georgios; Hoy, James J; Lokeshwar, Bal L (2016) Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Semin Cancer Biol 40-41:160-169|
|Shamaladevi, Nagarajarao; Araki, Shinako; Lyn, Dominic A et al. (2016) The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer. Oncotarget 7:84201-84213|
|Block, Keith I; Gyllenhaal, Charlotte; Lowe, Leroy et al. (2015) Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol 35 Suppl:S276-S304|
|Samadi, Abbas K; Bilsland, Alan; Georgakilas, Alexandros G et al. (2015) A multi-targeted approach to suppress tumor-promoting inflammation. Semin Cancer Biol 35 Suppl:S151-S184|
|Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K et al. (2015) Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. Oncotarget 6:16379-95|
|Salazar, Nicole; Muñoz, Daniel; Hoy, James et al. (2014) Use of shRNA for stable suppression of chemokine receptor expression and function in human cancer cell lines. Methods Mol Biol 1172:209-18|
|Salazar, Nicole; Muñoz, Daniel; Kallifatidis, Georgios et al. (2014) The chemokine receptor CXCR7 interacts with EGFR to promote breast cancer cell proliferation. Mol Cancer 13:198|
|Salazar, Nicole; Castellan, Miguel; Shirodkar, Samir S et al. (2013) Chemokines and chemokine receptors as promoters of prostate cancer growth and progression. Crit Rev Eukaryot Gene Expr 23:77-91|
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