Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Inhibitory effect of Korean Red Ginseng extract on DNA damage response and apoptosis in Helicobacter pylori-infected gastric epithelial cells

  • Kang, Hyunju (Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University) ;
  • Lim, Joo Weon (Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University) ;
  • Kim, Hyeyoung (Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University)
  • Received : 2017.09.29
  • Accepted : 2018.08.08
  • Published : 2020.01.15
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Abstract

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

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