Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells
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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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].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [138]
Cites
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Zou, L., & Elledge, S. J. (2003) · Science · doi:10.1126/science.1083430 · Cited by 2,693 · see citing works
Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo
Rogakou, E. P., Boon, C., Redon, C., & Bonner, W. M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.5.905 · Cited by 2,422 · see citing works
Lycopene as the most efficient biological carotenoid singlet oxygen quencher
Mascio, P. D., Kaiser, S., & Sies, H. (1989) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(89)90467-0 · Cited by 2,238 · see citing works
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966 · see citing works
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., & Chen, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100466200 · Cited by 1,954 · see citing works
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798 · see citing works
Chk2/hCds1 functions as a DNA damage checkpoint in G<sub>1</sub>by stabilizing p53
Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000) · Genes & Development · doi:10.1101/gad.14.3.278 · Cited by 805 · see citing works
DNA damage responses to oxidative stress
Barzilai, A., & Yamamoto, K.-I. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.03.002 · Cited by 796 · see citing works
Identification of a p53-dependent negative response element in the bcl-2 gene.
Miyashita, T., Harigai, M., Hanada, M., & Reed, J. C. (1994) · PubMed · Cited by 746 · see citing works
Levy, J., Bosin, E., Feldman, B., Giat, Y., Miinster, A., Danilenko, M., & Sharoni, Y. (1995) · Nutrition and Cancer · doi:10.1080/01635589509514415 · Cited by 507 · see citing works
Prevention of coronary heart disease.
British Medical Journal Publishing Group (1976) · BMJ · doi:10.1136/bmj.1.6014.881 · Cited by 383 · see citing works
Decker, P., & Muller, S. (2002) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201023378265 · Cited by 245 · see citing works
Lycopene, Tomatoes, and the Prevention of Coronary Heart Disease
Rao, A. V. (2002) · Experimental Biology and Medicine · doi:10.1177/153537020222701011 · Cited by 226 · see citing works
Porrini, M., & Riso, P. (2000) · Journal of Nutrition · doi:10.1093/jn/130.2.189 · Cited by 194 · see citing works
Regulation of p53 Tumor Suppressor by Helicobacter pylori in Gastric Epithelial Cells
Wei, J., Nagy, T. A., Vilgelm, A. E., Zaika, E. I., Ogden, S. R., Romero–Gallo, J., Piazuelo, M. B., Correa, P., Washington, M. K., El-Rifai, W. M., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.018 · Cited by 190 · see citing works
Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils.
Craig, P. M., Territo, M., Karnes, W. E., & Walsh, J. H. (1992) · Gut · doi:10.1136/gut.33.8.1020 · Cited by 180 · see citing works
Lycopene: A Review of Its Potential as an Anticancer Agent
Bhuvaneswari, V., & Nagini, S. (2005) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/156801105774574667 · Cited by 152 · see citing works
Huaier aqueous extract inhibits proliferation of breast cancer cells by inducing apoptosis
Zhang, N., Kong, X., Yan, S., Yuan, C., & Yang, Q. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01680.x · Cited by 128 · see citing works
ATM and ATR: Sensing DNA damage
Yang, J. J., Xu, Z., Huang, Y., Hamrick, H. E., Duerksen-Hughes, P. J., & Yu, Y. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i2.155 · Cited by 127 · see citing works
Tabak, Ö., Gelışgen, R., Erman, H., Erdenen, F., MÜDERRİSOĞLU, C., Aral, H., & Uzun, H. (2011) · Clinical and investigative medicine · doi:10.25011/cim.v34i3.15189 · Cited by 125 · see citing works
Palozza, P., Simone, R. E., Catalano, A., Boninsegna, A., Böhm, V., Fröhlich, K., Mele, M. C., Monego, G., & Ranelletti, F. O. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2008.10.002 · Cited by 115 · see citing works
Reddy, L., Odhav, B., & Bhoola, K. D. (2006) · Biological Chemistry · doi:10.1515/bc.2006.012 · Cited by 113 · see citing works
Srinivasan, M., Sudheer, A. R., Pillai, K. R., Kumar, P. R., Sudhakaran, P. R., & Menon, V. P. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.11.008 · Cited by 105 · see citing works
Regulation of the cellular DNA double-strand break response
Cann, K. L., & Hicks, G. G. (2007) · Biochemistry and Cell Biology · doi:10.1139/o07-135 · Cited by 101 · see citing works
Song, J. Y., Lim, J. W., Kim, H., Morio, T., & Kim, K. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303692200 · Cited by 99 · see citing works
Self-citationSeo, J. H., Lim, J. W., Kim, H., & Kim, K. H. (2003) · Laboratory Investigation · doi:10.1038/labinvest.3700010 · Cited by 95 · see citing works
Self-citationKim, H., Seo, J. Y., & Kim, K. H. (2000) · Digestive Diseases and Sciences · doi:10.1023/a:1005474013988 · Cited by 76 · see citing works
Self-citationTang, X., Yang, X., Peng, Y., & Lin, J. (2009) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-009-6206-3 · Cited by 76 · see citing works
Tomato Consumption Modulates Oxidative DNA Damage in Humans
Rehman, A., Bourne, L., Halliwell, B. B., & Rice-Evans, C. A. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1235 · Cited by 76 · see citing works
NF-κB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection
Lim, J. W., Kim, H., & Kim, K. H. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00592-5 · Cited by 74 · see citing works
Self-citationLuo, C., & Wu, X. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12053340 · Cited by 63 · see citing works
Helicobacter pylori inhibits gastric cell cycle progression
Ahmed, A., Smoot, D. T., Littleton, G. K., et al. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)01270-3 · Cited by 59 · see citing works
Sh, J., Jw, L., & Kim, H. (2009) · PubMed · Cited by 54 · see citing works
Self-citationKim, H., Seo, J., & Kim, K. H. (1999) · Pharmacology · doi:10.1159/000028321 · Cited by 46 · see citing works
Self-citationHelicobacter pylori γ-glutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition
Kim, K., Lee, S., Kim, J., Kim, D.-S., Song, J.-Y., Kang, H., Lee, W., Cho, M.-J., Rhee, K., Youn, H., et al. (2010) · The Journal of Microbiology · doi:10.1007/s12275-010-9293-8 · Cited by 46 · see citing works
Role of Helicobacter pylori CagA + Infection in Determining Oxidative DNA Damage in Gastric Mucosa
Papa, A., Danese, S., Sgambato, A., Ardito, R., Zannoni, G., Rinelli, A., Vecchio, F. M., Gentiloni-Silveri, N., Cittadini, A. R. M., Gasbarrini, G. B., et al. (2002) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655202317316033 · Cited by 45 · see citing works
Cha, B., Lim, J. W., Kim, K. H., & Kim, H. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.04.015 · Cited by 37 · see citing works
Self-citationCha, B., Lim, J. W., Kim, K. H., et al. (2011) · PubMed · Cited by 36 · see citing works
Self-citationSommi, P. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5629 · Cited by 31 · see citing works
Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage.
Muzandu, K. M., Bohi, K. E., Shaban, Z., Ishizuka, M., Kazusaka, A., & Fujita, S. (2005) · PubMed · doi:10.14943/jjvr.52.4.173 · Cited by 31 · see citing works
Protective Effect of Lycopene on Oxidative Stress‐Induced Cell Death of Pancreatic Acinar Cells
Seo, J. Y., Masamune, A., Shimosegawa, T., et al. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04712.x · Cited by 29 · see citing works
Chu, S. H., Lim, J. W., Kim, D. G., Lee, E.-S., Kim, K. H., & Kim, H. (2010) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2010.525255 · Cited by 29 · see citing works
Self-citationLycopene inhibits IL-6 expression in cerulein-stimulated pancreatic acinar cells
Kang, M., Park, K. S., Seo, J. Y., et al. (2010) · Genes & Nutrition · doi:10.1007/s12263-010-0195-5 · Cited by 28 · see citing works
Seo, J. Y., Kim, H., & Kim, K. H. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04697.x · Cited by 27 · see citing works
Self-citationEffects of H. pylori infection of gastric epithelial cells on cell cycle control
Shirin, H. (2001) · Frontiers in bioscience · doi:10.2741/shirin · Cited by 21 · see citing works
Petersson, F., Borch, K., & Franzén, L. (2002) · Digestive Diseases and Sciences · doi:10.1023/a:1015938303993 · Cited by 17 · see citing works
Chiou, C.-C., Chan, C. C., Kuo, Y.-P., et al. (2003) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520310000627 · Cited by 14 · see citing works
[Helicobacter pylori inhibits cell growth and induces G1/S arrest in AGS gastric epithelial cells].
Gao, W. H., Hu, F.-L., & Lu, Y. (2003) · PubMed · Cited by 2 · see citing works
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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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