Abstract A72: Efficacy and safety of multiple doses of polyphenon E in prostate cancer using TRAMP mice

Abstract

Abstract Purpose: The purpose of this study was to assess the efficacy and safety of polyphenon E as a chemopreventive agent against prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) mice model. Experimental Design: Seven week old 128 male control C57BL/6 mice and 128 male TRAMP mice were treated with 3 different doses of polyphenon E orally at a human achievable dose. Animals were sacrificed at 12, 22, and 32 weeks of age. For the safety study, complete blood counts with leukocyte differentials and blood chemistry levels for liver and kidney functions were determined. For the efficacy study, weight of the prostate, tumor progression and metastasis, and histopathological evaluation of all organs were assessed. Prostate histology was assessed separately for each lobe of the prostate (i.e., the anterior, dorsal, lateral, and ventral lobes) since lesions progress differently in each lobe of the mouse. Results: Polyphenon E treatment significantly inhibited prostate cancer progression and metastasis in TRAMP mice model. As expected, metastases were observed in all untreated TRAMP mice (100%, 8 of 8) at 32 weeks of age. However, significant reductions were found in all three polyphenon E treated groups with a dose response manner. 50% (6 of 12), 27% (3 of 11), and 12.5% (2 of 12) of low, intermediate, and high dose treated groups exhibited metastasis of prostate cancer to distant organ sites, respectively. Furthermore, treated TRAMP mice resulted in significant delay in tumor progression from 12 to 32 weeks of age with a dose response manner. No adverse effect in polyphenon E treatment group was found in control C57BL/6 mice up to 32 weeks of age regardless amount of polyphenone E treatment. Conclusion: Polyphenon E was an effective chemopreventive agent in the progression of prostate cancer in the animal model. Polyphenon E also showed minimal toxicity in the mice model. Citation Format: Jick Hwan Ha, Seung Joon Kim, Hea Yon Lee, Chang Dong Yeo, Chan Kwon Park, Sang Haak Lee, Jong Y. Park. Efficacy and safety of multiple doses of polyphenon E in prostate cancer using TRAMP mice. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A72.