title: Curcumin abrogates bile-induced NF-κB activity and DNA damage in vitro and suppresses NF-κB activity whilst promoting apoptosis in vivo, suggesting chemopreventative potential in Barrett's oesophagus.
abstract: BACKGROUND
  Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression.
  
  
  METHODS
  We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin.
  
  
  RESULTS
  In vitro, curcumin (50 μM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 μM) completely abolished the ability of DCA (300 μM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients.
  
  
  CONCLUSIONS
  Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.
authors.affiliation: Department of Surgery, Morriston Hospital, ABM University NHS Trust, Morriston, Swansea, UK.
authors.forename: N
authors.initials: N
authors.lastname: Rawat
authors.forename: A
authors.initials: A
authors.lastname: Alhamdani
authors.forename: E
authors.initials: E
authors.lastname: McAdam
authors.forename: J
authors.initials: J
authors.lastname: Cronin
authors.forename: Z
authors.initials: Z
authors.lastname: Eltahir
authors.forename: P
authors.initials: P
authors.lastname: Lewis
authors.forename: P
authors.initials: P
authors.lastname: Griffiths
authors.forename: J N
authors.initials: JN
authors.lastname: Baxter
authors.forename: G J S
authors.initials: GJ
authors.lastname: Jenkins
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001471:Barrett Esophagus / Q000188:drug therapy / Q000473:pathology*; D001646:Bile / Q000737:chemistry; D001706:Biopsy; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D016328:NF-kappa B; D003474:Curcumin