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Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model
Author(s) -
Venier Natalie A.,
Yamamoto Toshihiro,
Sugar Linda M.,
Adomat Hans.,
Fleshner Neil E.,
Klotz Laurence H.,
Venkateswaran Vasundara
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23013
Subject(s) - tramp , medicine , capsaicin , adenocarcinoma , prostate , prostate cancer , pathology , genetically modified mouse , gastroenterology , concomitant , saline , intraepithelial neoplasia , urology , endocrinology , cancer , transgene , biology , receptor , biochemistry , gene
BACKGROUND Capsaicin, the active compound in chili peppers, has demonstrated anti‐ carcinogenic properties in vitro in a number of malignancies, including the prostate. In the present study, we investigate the chemopreventive potential of capsaicin on prostate cancer using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The TRAMP is a murine model that resembles the progression of human disease. METHODS Thirty‐five 6‐week‐old TRAMP x C57BL/6 mice were randomized between treatment with capsaicin (5 mg/kg body weight) or control (saline) three times a week by oral gavage until 30 weeks of age. Body weight of animals was recorded thrice weekly. At termination, all tumors were extracted, recorded, and analyzed for histopathological analysis. To understand the effect of capsaicin on migration and invasion, in vitro experiments were carried out using PC3 cells. RESULTS Mice in the control group expressed an overall trend of higher‐grade disease with 37.5% poorly differentiated (PD), 18.75% moderately differentiated (MD), and 44% of well‐differentiated (WD) adenocarcinoma, compared to the capsaicin‐treated group with only 27.7% PD, 61.0% of WD, and 11.1% of intraepithelial neoplasia (PIN). The treatment group demonstrated a higher incidence of noncancerous PIN lesions compared to the control group. The capsaicin group also demonstrated a significant reduction ( P < 0.05) in the metastatic burden compared to the controls, which correlated to a reduction in p27 Kip 1 expression and neuroendocrine differentiation in prostate tumors. Furthermore, there were no differences in body weight between groups overtime, and no pathological toxicities in the liver and gastrointestinal tract with capsaicin consumption. In vitro studies revealed a dose‐dependent reduction in the invasion and migration capacity of PC3 cells. CONCLUSION The following study provides evidence supporting the safety and chemopreventive effects of capsaicin in the TRAMP model. Prostate 75:1300–1311, 2015 . © 2015 Wiley Periodicals, Inc.