title: Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model.
abstract: 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.
  
  
  CONCLUSIONS
  The following study provides evidence supporting the safety and chemopreventive effects of capsaicin in the TRAMP model.
authors.affiliation: Department of Surgery (Urology), Sunnybrook Health Sciences Center, Toronto, Ontario.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Venier
authors.affiliation: Department of Surgery (Urology), Sunnybrook Health Sciences Center, Toronto, Ontario.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Pathology, Sunnybrook Health Sciences Center, Toronto, Ontario.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Sugar
authors.affiliation: Department of Analytical Pharmacology, Vancouver Prostate Group, Vancouver, British Columbia.
authors.forename: Hans
authors.initials: H
authors.lastname: Adomat
authors.affiliation: Department of Surgery (Urology), University Health Network, Princess Margaret Hospital, Toronto, Ontario.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
authors.affiliation: Department of Surgery (Urology), Sunnybrook Health Sciences Center, Toronto, Ontario.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.affiliation: Department of Surgery (Urology), Sunnybrook Health Sciences Center, Toronto, Ontario.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018689:Sensory System Agents / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: D016588:Anticarcinogenic Agents; D018689:Sensory System Agents; D002211:Capsaicin
keywords: capsaicin; invasion; metastasis; migration; prostate cancer; transgenic mice