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Hydrogen peroxide and Helicobacter pylori extract treatment combined with APE1 knockdown induce DNA damage, G2/M arrest and cell death in gastric cancer cell line

dc.contributor.authorManoel-Caetano, Fernanda S. [UNESP]
dc.contributor.authorRossi, Ana Flávia T. [UNESP]
dc.contributor.authorRibeiro, Marcelo Lima
dc.contributor.authorPrates, Janesly [UNESP]
dc.contributor.authorOliani, Sonia Maria [UNESP]
dc.contributor.authorSilva, Ana Elizabete [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionSão Francisco University
dc.date.accessioned2021-06-25T11:05:19Z
dc.date.available2021-06-25T11:05:19Z
dc.date.issued2020-12-01
dc.description.abstractChronic inflammation resulting from Helicobacter pylori (H. pylori) infection, the major risk factor for gastric cancer, results in increased release of reactive oxygen species (ROS), promoting oxidative stress and DNA damage. APE1 endonuclease, a key component of the base excision repair (BER) pathway, is responsible for the repair of damage induced by ROS. However, the APE1 gene and other DNA damage response (DDR) genes are still poorly understood in gastric cancer. Thus, we aimed to investigate whether the silencing of APE1 by shRNA can interfere with the survival of AGS gastric cancer cells after treatment with hydrogen peroxide (H2O2) and/or H. pylori extract (HPE) and its relation with the expression of DDR genes (ATM, ATR, and H2AX) and miRNAs that target DDR genes. In the AGS cells expressing APE1, isolated or combined treatment with H2O2 and HPE promoted a slight increase in the cell proliferation and increased the levels of intracellular ROS and DNA double strand breaks (DSBs) indicated by ©H2AX foci, a reduction in the proportion of cells in the G0/G1 phase and an increase in the initial apoptosis rate. Moreover, upregulation of APE1, ATR, miR-15a, miR-21, miR-24 and miR-421 and downregulation of ATM and H2AX was observed. In silenced AGS cells after treatment with H2O2 alone or combined with HPE, we observed an increase in the cell proliferation rate and the levels of intracellular ROS and DSBs and a reduction in the proportion of cells in S and G2/M phase arrest, leading to late apoptosis. APE1 knockdown also caused a reduction in the expression of ATM and miR-421, while ATR expression was increased. Based on our results, APE1 knockdown may promote changes in cellular processes by increasing genomic instability, leading to G2/M arrest and cell apoptosis, so it may be a promising strategy for controlling tumor progression.en
dc.description.affiliationDepartment of Biology UNESP São Paulo State University
dc.description.affiliationClinical Pharmacology and Gastroenterology Unit São Francisco University
dc.description.affiliationUnespDepartment of Biology UNESP São Paulo State University
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCAPES: 1460154
dc.description.sponsorshipIdFAPESP: 2015/21464-0
dc.description.sponsorshipIdCNPq: 310120/2015-2
dc.identifierhttp://dx.doi.org/10.1016/j.dnarep.2020.102976
dc.identifier.citationDNA Repair, v. 96.
dc.identifier.doi10.1016/j.dnarep.2020.102976
dc.identifier.issn1568-7856
dc.identifier.issn1568-7864
dc.identifier.scopus2-s2.0-85092386388
dc.identifier.urihttp://hdl.handle.net/11449/208037
dc.language.isoeng
dc.relation.ispartofDNA Repair
dc.sourceScopus
dc.subjectAGS cell line
dc.subjectAPE1 knockdown
dc.subjectDNA damage
dc.subjectDNA repair
dc.subjectHelicobacter pylori
dc.subjectHydrogen peroxide
dc.titleHydrogen peroxide and Helicobacter pylori extract treatment combined with APE1 knockdown induce DNA damage, G2/M arrest and cell death in gastric cancer cell lineen
dc.typeArtigo
dspace.entity.typePublication
unesp.campusUniversidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt
unesp.departmentBiologia - IBILCEpt

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