Helicobacter pylori inhibits activity of cdc2 kinase and delays G₂/M to G₁ progression in gastric adenocarcinoma cell line

Background: Helicobacter pylori is a bacterial pathogen strongly associated with ulcer diseases and gastric cancer. The bacterial-induced alteration of cell-cycle control in host cells may play a role in the pathogenetic mechanisms. The aims of this study were to define the effect of H. pylori on the G₂/M to G₁ transition in a gastric cell line. Methods: Cultured gastric cells, AGS, were synchronized in the S/early G2 phase and treated with intact H. pylori. The cell-cycle distribution of AGS cells was determined by flow cytometry. The activity of cdc2 kinase, as well as of some parameters that affect the kinase activity, was also examined. Results: H. pylori delays cell-cycle progression at the G₂/M phase in AGS cells. The G₂/M delay was associated with reduced activity of cdc2 kinase. Both down-regulation of cell-cycle regulators (p34^cdc2, cyclin B1 and cdc25C) and decreased association between p34^cdc2 and cyclin B1 were found to be associated with the activity of cdc2 kinase abated after the H. pylori infection. In addition, the H. pylori-induced G₂/M delay required direct contact between the bacteria and host cells. Conclusions: H. pylori inhibits G₂/M to G₁ progression and causes a reduction of cell division in gastric epithelial cells.