Inhibitory effect of Korean Red Ginseng extract on DNA damage response and apoptosis in-infected gastric epithelial cells.
J Ginseng Res. 2020 Jan ;44(1):79-85. Epub 2018 Aug 14. PMID: 32148392
Background: 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,-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-infected gastric epithelial cells.
Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in-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: induced apoptosis by increasing apoptotic indices and ROS levels.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-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in-infected gastric epithelial cells, similar to KRG.
Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated withinfection.