Helicobacter Pylori Causes Oxidative Stress and Apoptosis in DNA Double Strand Break Repair Inhibited Human Gastric Adenocarcinoma Cells

Abstract

Helicobacter pylori, a helix-shaped gram-negative microaerophilic bacteria has been classified as a human carcinogen (Group I carcinogen) by the International Agency for Research on Cancer (IARC) on the basis of numerous animal and epidemiological studies. Chronic Helicobacter pylori infection can cause lead to high levels of intracellular reactive oxygen species (ROS) and genomic instability both directly by genetic and/or epigenetic pathways. It is known that high levels of intracellular ROS can trigger apoptosis and induce DSBs. In this study, we aimed to investigate intracellular ROS levels and apoptotic effects of Helicobacter pylori infection on AGS cells in the presence of a DSB repair inhibitor [8-(4-dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one, Nu7441]. After incubation of AGS cells with different multiplicities of infection (MOIs; 25, 50, 75, 100, 200 and 400), we observed that Helicobacter pylori causes MOI-dependent cytotoxicity and intracellular ROS levels significantly increased in all study groups vs. control. Both caspase 3 and caspase 8 levels were higher all of the study group when compared to control group. In HP+Nu7441 group, caspase 8 levels 3.5 times higher vs. control; indicating unrepaired DSBs in Helicobacter pylori infection can highly be induce apoptosis in AGS cells. Other cell death mechanisms, including autophagy, should be studies in order to fully understand the cytotoxicity mechanisms of the bacterium. Moreover, we can state that in organisms with unrepaired DSBs or with high DSB levels, Helicobacter pylori can cause more oppressive adverse effects, the importance of which should be elucidated with mechanistic studies.

Keywords

• Helicobacter pylori
• AGS cells
• gastric carcinoma
• reactive oxygen species
• apoptosis