Cited by 62DNA Repair MechanismsHelicobacter pylori-related gastroenterology studiesAntioxidant Activity and Oxidative Stress

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

Jang, Sung Hee, Lim, Joo Weon, Morio, Tomohiro, Kim, Hyeyoung·2012·Free Radical Biology and Medicine

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.

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Crossref · 10.1016/j.freeradbiomed.2011.11.010

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  • Lycopene inhibits H. pylori-induced gastric diseases associated with oxidative DNA damage such as 8-OH-G and double-strand breaks and prevents ROS-induced ATM- and ATR-mediated DNA damage response in gastric epithelial AGS cells.

    “In addition, the natural antioxidant Lycopene inhibits H. pylori-induced gastric diseases associated with oxidative DNA damage (e.g., 8–OH–G and DSBs) and prevents ROS-induced ATM- and ATR-mediated DDR in gastric epithelial AGS cells [138].”

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Authors
Jang, S. H., Lim, J. W., Morio, T., & Kim, H.
Affiliations
  • Yonsei University (KR)
  • Tokyo Medical and Dental University (JP)
Corresponding author
  • Morio, Tomohiro
  • Kim, Hyeyoung
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2012-02
Volume
52
Issue
3
Pages
607-615
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2019297458
Cited by
62
References
48
Citations by year
2026: 1 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 2
FWCI
1.30
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Science and Technology (2010–0002916, 2011–0001177, F01-2009-000-10101-0)
  • Japan Society for the Promotion of Science
  • National Research Foundation of Korea
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
lycopene, Helicobacter pylori, DNA damage response, ATM, ATR, oxidative DNA damage, reactive oxygen species, apoptosis, gastric epithelial cells, DNA double-strand breaks, p53, Chk1, Chk2, histone H2AX, Bax/Bcl-2 ratio, PARP1, cell cycle arrest, antioxidants, gastric diseases
MeSH terms
Lycopene, Carotenoids, Cell Cycle, Cell Line, Cell Survival, DNA-Binding Proteins, Epithelial Cells, Gastric Mucosa, Humans, Phosphorylation, Free Radical Scavengers, Helicobacter pylori, Helicobacter Infections, Apoptosis, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Oxidative Stress, Cell Cycle Proteins, Tumor Suppressor Proteins, Cell Proliferation, Apoptosis Regulatory Proteins, DNA Fragmentation, Ataxia Telangiectasia Mutated Proteins

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