title: Capsaicin: a novel radio-sensitizing agent for prostate cancer.
abstract: BACKGROUND
  Radio-sensitizing agents sensitize tumor cells to the lethal effects of radiotherapy (RT) allowing for use of lower doses of radiation to achieve equivalent cancer control, while minimizing adverse effects to normal tissues. Given their limited toxicity and ability to easily integrate into the diet, compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. In this study, we have examined whether capsaicin, the active compound in chilli peppers, can modulate the response to RT in preclinical models of prostate cancer (PCa).
  
  
  METHODS
  The effects of RT (1-8 Gy) and/or capsaicin (1-10 µM) on colony formation rates in human PCa cells were assessed using clonogenic assays. Mechanistic studies were performed by Western Blot, immunocytochemistry, and flow cytometry. Athymic mice (n = 40) were inoculated with human LNCaP cells. Once tumors reached 100 mm(3) , animals were randomized into four groups: control, capsaicin alone (5 mg/kg/d), RT alone (6 Gy), and capsaicin and RT.
  
  
  RESULTS
  Capsaicin reduced colony formation rates and radio-sensitized human PCa cells (Sensitizer enhancement ratio = 1.3) which corresponded to the suppression of NFκB, independent of TRP-V1 receptor. Cell cycle modulation occurred following RT and capsaicin treatment independently. In vivo, oral administration of capsaicin with RT resulted in a 'greater than additive' growth delay and reduction in the tumor growth rate greater than capsaicin (P < 0.001) or RT (P < 0.03) alone. Immunohistochemical analysis revealed a reduction in proliferation and NFκB expression, and increase in DNA damage.
  
  
  CONCLUSIONS
  Our findings suggest that capsaicin acts as a radio-sensitzing agent for PCa through the inhibition of NFκB signalling.
authors.affiliation: Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Venier
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Colquhoun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Alex
authors.initials: A
authors.lastname: Kiss
authors.forename: Linda
authors.initials: L
authors.lastname: Sugar
authors.forename: Hans
authors.initials: H
authors.lastname: Adomat
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D011838:Radiation-Sensitizing Agents; D002211:Capsaicin
keywords: NFκB signalling; capsaicin; natural compound; prostate neoplasm; radiation; radiosenisitizing agent; therapeutic ratio