Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells

Sung Hee Jang, Joo Weon Lim, Tomohiro Morio, Hyeyoung Kim

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Oxidative stress linked to DNA damage is involved in the pathogenesis of Helicobacter pylori-associated gastric diseases. The DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair, and apoptosis through the activation of ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) and their target proteins. However, neither H. pylori-induced DDR nor the effects of antioxidants on the DNA damage have been established. This study aimed to investigate the detailed process of H. pylori-induced DNA damage and to examine whether lycopene, a natural antioxidant, inhibits DNA damage and cellular response of gastric epithelial AGS cells infected with H. pylori. AGS cells were cultured with H. pylori in Korean isolates and treated with or without lycopene. Cell viability, DNA damage indices, levels of 8-OH-dG, and reactive oxygen species (ROS) as well as cell-cycle distributions were determined. The activation of ATM, ATR, Chk1, and Chk2; histone H2AX focus formation; activation and induction of p53; and levels of Bax and Bcl-2 and poly(ADP-ribose) polymerase-1 (PARP-1) were assessed. The results showed that H. pylori induced apoptosis in AGS cells with increased Bax and decreased Bcl-2 expression as well as PARP-1 cleavage. Culture with H. pylori led to increases in intracellular ROS, 8-OH-dG, double-strand DNA breaks (DSBs), and DNA fragmentation. H. pylori induced activation of the ATM/Chk2 and ATR/Chk1 pathways, phosphorylation of H2AX and p53, and a delay in the progression of the cells entering the S phase. Lycopene inhibited H. pylori-induced increases in ROS, apoptosis, alterations in cell-cycle distribution, DSBs, and ATM- and ATR-mediated DDR in AGS cells. In conclusion, lycopene may be beneficial for treatment of H. pylori-induced gastric diseases associated with oxidative DNA damage.

Original languageEnglish
Pages (from-to)607-615
Number of pages9
JournalFree Radical Biology and Medicine
Volume52
Issue number3
DOIs
Publication statusPublished - 2012 Feb 1

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2010–0002916, 2011–0001177) and by a grant (Joint Research Project under the Korea–Japan Basic Scientific Cooperation Program) from the NRF (F01-2009-000-10101-0) (to H.K.) and from the JSPS (to T.M.).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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