Source
Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
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.
MATERIALS AND 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.
CONCLUSION:
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.