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Oxidative Stress Promotes Doxorubicin-Induced Pgp and BCRP Expression in Colon Cancer Cells Under Hypoxic Conditions

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dc.creatorPinzón-Daza M.L.spa
dc.creatorCuellar-Saenz Y.spa
dc.creatorNualart F.spa
dc.creatorOndo Méndez, Alejandro Oyonospa
dc.creatorDel Riesgo Prendes, Liliaspa
dc.creatorCastillo-Rivera F.spa
dc.creatorGarzón R.spa
dc.date.accessioned2020-05-25T23:55:58Z
dc.date.available2020-05-25T23:55:58Z
dc.date.created2017spa
dc.description.abstractP-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1? activity via ELISA, Pgp, and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR). These cells were treated with doxorubicin and/or CoCl2 (chemical hypoxia), and reactive oxygen species inductors. We found that the combination of chemically induced hypoxia and doxorubicin promoted Pgp mRNA expression within 24 h in HT-29WT and HT-29DxR cells. Both doxorubicin and CoCl2 alone or in combination induced Pgp and BCRP expression, as demonstrated via confocal microscopy in each of the above two cell lines. Thus, we surmised that Pgp and BCRP expression may result from synergistic effects exerted by the combination of doxorubicin-induced ROS production and HIF-1? activity under hypoxic conditions. However, HIF-1? activity disruption via the administration of E3330, an APE-1 inhibitor, downregulated Pgp expression and increased doxorubicin delivery to HT-29 cells, where it served as a substrate for Pgp, indicating the existence of an indirect relationship between Pgp expression and doxorubicin accumulation. Thus, we concluded that Pgp and BCRP expression can be regulated via cross-talk between doxorubicin and hypoxia, promoting drug resistance in HT-29 WT, and HT-29DxR cells and that this process may be ROS dependent. J. Cell. Biochem. 118: 1868–1878, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1002/jcb.25890
dc.identifier.issn07302312
dc.identifier.issn10974644
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22281
dc.language.isoengspa
dc.publisherWiley-Liss Inc.spa
dc.relation.citationEndPage1878
dc.relation.citationIssueNo. 7
dc.relation.citationStartPage1868
dc.relation.citationTitleJournal of Cellular Biochemistry
dc.relation.citationVolumeVol. 118
dc.relation.ispartofJournal of Cellular Biochemistry, ISSN:07302312, 10974644, Vol.118, No.7 (2017); pp. 1868-1878spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85016408376&doi=10.1002%2fjcb.25890&partnerID=40&md5=c8ea706c4f4602b9071bd60fd2284487spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordBreast cancer resistance proteinspa
dc.subject.keywordconfocaleng
dc.subject.keywordtumoreng
dc.subject.keywordhumaneng
dc.subject.keywordhumaneng
dc.subject.keywordhumaneng
dc.subject.keywordalpha subuniteng
dc.subject.keywordCobalt chloridespa
dc.subject.keywordsub-family geng
dc.subject.keywordsub-family beng
dc.subject.keywordmember 1eng
dc.subject.keywordmember 2eng
dc.subject.keywordDoxorubicinspa
dc.subject.keywordE 3330spa
dc.subject.keywordHypoxia inducible factor 1alphaspa
dc.subject.keywordLyase inhibitorspa
dc.subject.keywordMultidrug resistance proteinspa
dc.subject.keywordReactive oxygen metabolitespa
dc.subject.keywordUnclassified drugspa
dc.subject.keywordAbcg2 proteineng
dc.subject.keywordApex1 proteineng
dc.subject.keywordBreast cancer resistance proteinspa
dc.subject.keywordDna (apurinic or apyrimidinic site) lyasespa
dc.subject.keywordDoxorubicinspa
dc.subject.keywordHif1a proteineng
dc.subject.keywordHypoxia inducible factor 1alphaspa
dc.subject.keywordMultidrug resistance protein 1spa
dc.subject.keywordTumor proteinspa
dc.subject.keywordArticlespa
dc.subject.keywordCancer growthspa
dc.subject.keywordCancer resistancespa
dc.subject.keywordCancer survivalspa
dc.subject.keywordColon cancerspa
dc.subject.keywordConfocal microscopyspa
dc.subject.keywordControlled studyspa
dc.subject.keywordEnzyme linked immunosorbent assayspa
dc.subject.keywordHt-29 cell linespa
dc.subject.keywordHumanspa
dc.subject.keywordHuman cellspa
dc.subject.keywordHypoxiaspa
dc.subject.keywordOxidative stressspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein expressionspa
dc.subject.keywordReverse transcription polymerase chain reactionspa
dc.subject.keywordCell hypoxiaspa
dc.subject.keywordCell survivalspa
dc.subject.keywordColon tumorspa
dc.subject.keywordDrug effectsspa
dc.subject.keywordGeneticsspa
dc.subject.keywordHt-29 cell linespa
dc.subject.keywordMetabolismspa
dc.subject.keywordOxidative stressspa
dc.subject.keywordPhysiologyspa
dc.subject.keywordTumor cell linespa
dc.subject.keywordAtp binding cassette transportereng
dc.subject.keywordAtp-binding cassetteeng
dc.subject.keywordCell hypoxiaspa
dc.subject.keywordCell lineeng
dc.subject.keywordCell survivalspa
dc.subject.keywordColonic neoplasmsspa
dc.subject.keywordDna-(apurinic or apyrimidinic site) lyasespa
dc.subject.keywordDoxorubicinspa
dc.subject.keywordEnzyme-linked immunosorbent assayspa
dc.subject.keywordHt29 cellsspa
dc.subject.keywordHumansspa
dc.subject.keywordHypoxia-inducible factor 1eng
dc.subject.keywordMicroscopyeng
dc.subject.keywordNeoplasm proteinsspa
dc.subject.keywordOxidative stressspa
dc.subject.keywordReactive oxygen speciesspa
dc.subject.keywordColon cancerspa
dc.subject.keywordDrug resistancespa
dc.subject.keywordP-glycoproteinspa
dc.subject.keywordReactive oxygen speciesspa
dc.titleOxidative Stress Promotes Doxorubicin-Induced Pgp and BCRP Expression in Colon Cancer Cells Under Hypoxic Conditionsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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