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Clinical and Translational Oncology

, Volume 14, Issue 4, pp 302–311 | Cite as

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

  • Nihit Rawat
  • Ali Alhamdani
  • Elizabeth McAdam
  • James Cronin
  • Zak Eltahir
  • Paul Lewis
  • Paul Griffiths
  • John N. Baxter
  • Gareth J. S. JenkinsEmail author
Research Articles

Abstract

Introduction

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.

Keywords

Barrett’s oesophagus Curcumin NF-κB 

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Copyright information

© Feseo 2012

Authors and Affiliations

  • Nihit Rawat
    • 1
  • Ali Alhamdani
    • 1
  • Elizabeth McAdam
    • 2
  • James Cronin
    • 2
  • Zak Eltahir
    • 2
  • Paul Lewis
    • 2
  • Paul Griffiths
    • 3
  • John N. Baxter
    • 1
  • Gareth J. S. Jenkins
    • 2
    Email author
  1. 1.Department of Surgery Morriston HospitalABM University NHS TrustMorriston, SwanseaUK
  2. 2.Institute of Life Science Swansea School of MedicineSwansea UniversitySingleton Park, SwanseaUK
  3. 3.Department of Histopathology Morriston HospitalABM University NHS TrustMorriston, SwanseaUK

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