論文 - 詳細
RRC ID | 19629 |
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著者 | Zaidi SF, Yamamoto T, Refaat A, Ahmed K, Sakurai H, Saiki I, Kondo T, Usmanghani K, Kadowaki M, Sugiyama T. |
タイトル | Modulation of activation-induced cytidine deaminase by curcumin in Helicobacter pylori-infected gastric epithelial cells. |
ジャーナル | Helicobacter |
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. |
巻・号 | 14(6) |
ページ | 588-95 |
公開日 | 2009-12-1 |
DOI | 10.1111/j.1523-5378.2009.00724.x |
PII | HEL724 |
PMID | 19889077 |
MeSH | Cell Line, Tumor Curcumin / metabolism* Cytidine Deaminase / genetics Cytidine Deaminase / metabolism* Down-Regulation Enzyme Activation Epithelial Cells / enzymology* Epithelial Cells / metabolism Epithelial Cells / microbiology Gastric Mucosa / cytology Gastric Mucosa / enzymology* Gastric Mucosa / metabolism Gastric Mucosa / microbiology Gene Expression Regulation, Enzymologic* Helicobacter Infections / enzymology* Helicobacter Infections / metabolism Helicobacter Infections / microbiology Helicobacter pylori / physiology* Humans |
IF | 4.0 |
引用数 | 35 |
WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY MICROBIOLOGY |
リソース情報 | |
ヒト・動物細胞 | MKN45(RCB1001) |