Digestive Diseases and Sciences

, Volume 53, Issue 3, pp 597–605

Effect of Adiponectin and Ghrelin on Apoptosis of Barrett Adenocarcinoma Cell Line

  • Peter C. Konturek
  • Grzegorz Burnat
  • Tilman Rau
  • Eckhart G. Hahn
  • Stanislaw Konturek
Original Paper

DOI: 10.1007/s10620-007-9922-1

Cite this article as:
Konturek, P.C., Burnat, G., Rau, T. et al. Dig Dis Sci (2008) 53: 597. doi:10.1007/s10620-007-9922-1

Abstract

Background Obesity is an important risk factor for Barrett adenocarcinoma. However, the role of adiponectin (anti-inflammatory adipokine from adipose tissue) and ghrelin (orexigenic peptide gastric origin) on the progression of Barrett’s carcinogenesis has not been investigated so far. The aim of the present study was: (1) to compare the expression of adiponectin and ghrelin receptors in Barrett’s esophagus and in normal squamous epithelium; (2) to assess the effect of adiponectin and ghrelin on apoptosis in Barrett’s adenocarcinoma cells in vitro; and (3) to investigate the effect of ghrelin on IL-1β and COX-2 expression in OE-19 cells incubated with TNFα. Methods The expression of ghrelin and adiponectin receptors (GHS-R1a, Adipo-R1, Adipo R-2) in biopsies from Barrett’s esophagus and in Barrett’s adenocarcinoma cell line OE-19 was assessed by quantitative RT-PCR (qRT-PCR). The OE-19 cells were also incubated with adiponectin (5–10 μg/ml), and the apoptosis and proliferation were assessed by FACS and MTT assays. Additionally, effects of adiponectin on the mRNA and protein expression of proapoptotic Bax and antiapoptotic Bcl-2 were assessed by RT-PCR and Western blot, respectively. In two different in vitro models of esophagitis the OE-19 cells were incubated with ghrelin alone or in the presence of TNFα or bile acids in the normal or pulse acidified medium, and the expression of IL-1β and COX-2 as markers for inflammation were assessed by FACS and qRT-PCR, respectively. Results Adiponectin caused a significant increase in apoptosis, and this affect was accompanied by increased Bax and decreased Bcl-2 expression. In contrast, ghrelin had no effect on apoptosis of OE-19 cells incubated in neutral or acidified medium with or without addition of deoxycholic acid. At the mRNA level, the expression of adiponectin receptors (Adipo-R1, Adipo-R2) was decreased, and the expression of ghrelin receptor (GHS-R1a) was increased in Barrett’s mucosa. Ghrelin caused a decrease in TNFα-induced COX-2 and IL-1β expression in OE-19 cells. Conclusion Adiponectin and ghrelin have an inhibitory effect on Barrett’s carcinogenesis by two different mechanisms: (1) by an increase in apoptosis by adiponectin, and (2) by anti-inflammatory actions of ghrelin. The decrease in levels of these two peptides in obesity may explain the progression of Barrett’s carcinoma in obese individuals.

Keywords

Adiponectin Ghrelin Barrett’s cancerogenesis Adipo-R1 Adipo-R2 TNFα IL-1β 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Peter C. Konturek
    • 1
  • Grzegorz Burnat
    • 1
  • Tilman Rau
    • 2
  • Eckhart G. Hahn
    • 1
  • Stanislaw Konturek
    • 3
  1. 1.First Department of MedicineUniversity Erlangen-NurembergErlangenGermany
  2. 2.Department of PathologyUniversity Erlangen-NurembergErlangenGermany
  3. 3.Institute of PhysiologyUniversity School of MedicineCracowPoland

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