title: Modulation of activation-induced cytidine deaminase by curcumin in Helicobacter pylori-infected gastric epithelial cells.
abstract: BACKGROUND
  Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori-infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-kappaB activation by H. pylori and hence, inhibition of NF-kappaB pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-kappaB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-kappaB inhibitory activity in H. pylori-infected gastric epithelial cells.
  
  
  METHODS
  MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-kappaB, inhibitors of NF-kappaB (IkappaB), and IkappaB kinase (IKK) complex regulation with or without curcumin.
  
  
  RESULTS
  The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (< or =10 micromol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-kappaB activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (< or =10 micromol/L) has suppressed H. pylori-induced NF-kappaB activation via inhibition of IKK activation and IkappaB degradation.
  
  
  CONCLUSIONS
  Nonbactericidal concentrations of curcumin downregulated H. pylori-induced AID expression in gastric epithelial cells, probably via the inhibition of NF-kappaB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori-related gastric carcinogenesis.
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Syed Faisal Haider
authors.initials: SF
authors.lastname: Zaidi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Alaa
authors.initials: A
authors.lastname: Refaat
authors.forename: Kanwal
authors.initials: K
authors.lastname: Ahmed
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Khan
authors.initials: K
authors.lastname: Usmanghani
authors.forename: Makoto
authors.initials: M
authors.lastname: Kadowaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D045744:Cell Line, Tumor; D003474:Curcumin / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D015971:Gene Expression Regulation, Enzymologic; D016481:Helicobacter Infections / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans
chemical_list: D003564:Cytidine Deaminase; D003474:Curcumin