Yuichi Akai

Green Tea Polyphenols Reduce Gastric Epithelial Cell Proliferation and Apoptosis Stimulated by Helicobacter pylori Infection

Recently the finding of gastric cancer in Helicobacter pylori (H. pylori)-infected mouse models was reported. Studies of humans and animal models have shown that H. pylori infection stimulates gastric epithelial cell proliferation and apoptosis. Polyphenols contained in green tea and related compounds were reported to have a variety anti-tumor effects and bactericidal properties. We studied the effect of green tea polyphenols on gastric cell proliferation and apoptosis in an H. pylori-infected mouse model. This model was prepared by inoculating Balb/c mice with 108 cfu of H. pylori (NCTC 11637 strain) by gavage. Beginning 18 weeks after inoculation, 0.5% polyphenols were given in drinking water every day for 2 weeks. Mice were sacrificed 1 h after bromodeoxyuridine (BrdU) was given i.p. for preparation of paraffin-embedded specimens. Cell proliferation and apoptosis were examined by the avidin-biotin complex method using anti-BrdU antibody and the TUNEL method, respectively. H. pylori infection resulted in increased BrdU-labeled cells in both the antrum and the bodies. Administration of polyphenols suppressed this increased proliferation. H. pylori infection increased apoptotic cells in both the antrum and the corpus in comparison with controls. This increase was not seen in H. pylori-infected mice given polyphenols. We conclude the administration with polyphenols might suppress gastric carcinogenesis that is in part related to H. pylori infection.

The expression of IGF-1R in Helicobacter pylori-infected intestinal metaplasia and gastric cancer.

Overexpression of IGF-1R has been demonstrated in gastrointestinal cancers, and its expression is reported as the result of the loss of tumor suppressors. IL-16 is involved in the pathophysiological process of chronic inflammatory diseases. The aim of this study is to determine the changes in the expression of IGF-1R in intestinal metaplasia (IM) and gastric cancer (GC) as well as the effect of Helicobacter pylori (H. pylori) and IL-16 on cell proliferation and IGF-1R expression in gastric cells. AGS cells were incubated with combinations of IL-16 and H. pylori. Gastric cell proliferation was studied by BrdU uptake. In H. pylori infected mucosa, IGF-1R was significantly higher in IM than chronic gastritis (CG), and also higher in GC than CG and IM. H. pylori significantly decreased BrdU uptake. IL-16 increased BrdU uptake and IGF-1R on AGS cells which had been decreased by H. pylori. Co-incubation with IL-16 increased the expression of IGF-1R mRNA in H. pylori infected cells. We conclude that the expression of IGF-1R in H. pylori infected gastric mucosa may indicate an early stage of carcinogenesis. The IL-16 secretion by H. pylori can be a trigger for the expression of IGF-1R, and it may also be a factor for gastric carcinogenesis.

Green tea polyphenols reduce gastric epithelial cell proliferation and apoptosis stimulated by Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection in the human stomach is associated with increased epithelial proliferation, and the increased proliferation is one of the risk factors for developing gastric carcinoma. Recently, cells undergoing apoptosis were found to be increased in human gastric mucosa in persons carrying H. pylori. Green tea polyphenols (polyphenols) have been reported to show a variety of biological activities against various foodborne pathological bacteria. Therefore, we studied the effect of polyphenols on gastric epithelial proliferation and apoptosis in H. pylori infected mice. Methods: We challenged Balb/C mice with I08cfu/mouse of the H. pylori (NCTC 11637) strain for 18 weeks. After this challenge, mice were treated with 0.5% polyphenols dairy in drinking water for 2 weeks, and given 5 mg/kg bromodeoxyuridine (BrdU) by introperitoneal injection, I hour before sacrify. Gastric epithelial cell proliferation was evaluated by immunohistochemical anti-BrdU labeling. Apoptosis was examined by using the Tunel method on tissue sections. Results: The number of BrdUlabeled cells in was significantly increased on the H. pylori challenged mice compared with control. The increased proliferation was reduced by polyphenols administration. The number of apoptosis cells also was increased in H. pylori challenged mice. The increased apoptosis was reduced by polyphenols administration. Conclusions: Green tea polyphenols reduced the gastric epithelial cell proliferation and apoptosis caused by H. pylori infection. Administration of green tea polyphenols may reduce gastric carcinogenesis induced by H. pylori infection. 2803