Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/69815
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dc.contributor.authorMartín-Rodríguez, Patriciaen_US
dc.contributor.authorGuerra, Borjaen_US
dc.contributor.authorHueso-Falcón, Idairaen_US
dc.contributor.authorAranda Tavío, Haidee Magdalenaen_US
dc.contributor.authorDíaz-Chico, Juanen_US
dc.contributor.authorQuintana Aguiar, José Martínen_US
dc.contributor.authorEstévez, Franciscoen_US
dc.contributor.authorDíaz-Chico, Bonifacioen_US
dc.contributor.authorAmesty, Angelen_US
dc.contributor.authorEstévez-Braun, Anaen_US
dc.contributor.authorFernández-Pérez, Leandroen_US
dc.date.accessioned2020-02-05T12:50:19Z-
dc.date.available2020-02-05T12:50:19Z-
dc.date.issued2019en_US
dc.identifier.issn1663-9812en_US
dc.identifier.otherScopus-
dc.identifier.otherWoS-
dc.identifier.urihttp://hdl.handle.net/10553/69815-
dc.description.abstractThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). BCR-ABL1-STAT5 is an oncogenic signaling pathway in human chronic myelogenous leukemia (CML) and it represents a valid target for anti-CML drug design. Resistance to direct BCR-ABL1 inhibitors is a common clinical issue, so STAT5 inhibition has become an interesting alternative target. In this study, the effects of NPQ-C6, a novel naphtoquinone-coumarin conjugate, were evaluated on human CML-derived K562 cells. Live-Cell Imaging analysis revealed that NPQ-C6 inhibited 2D (IC50AUC = 1.4 ± 0.6 μM) growth of CML cells. NPQ-C6 increased sub-G1 and reduced G0/G1 cell cycle phases in a dose- and time-dependent manner. This effect on cell cycle was related to increased levels of apoptotic nuclei, cleavage of caspase-3, -9, and PARP and annexin V-positive cells. NPQ-C6 increased γH2AX, a double-strand DNA break marker. NPQ-C6 showed a wide range of modulatory effects on cell signaling through an early increased phosphorylation of JNK, P38-MAPK and AKT, and decreased phosphorylation of ERK1/2, BCR-ABL1, and STAT5. NPQ-C6 inhibited expression of c-MYC and PYM-1, two target gene products of BCR-ABL1/STAT5 signaling pathway. Cytokine-induced activation of STAT5/STAT3-dependent transcriptional and DNA binding activities were also inhibited by NPQ-C6. Notably, NPQ-C6 maintained its activity on BCR-ABL1/STAT5/c-MYC/PIM-1 oncogenic pathway in imatinib-resistant cells. Molecular modeling suggested BCR-ABL1 and JAK2 proteins as NPQ-C6 targets. In summary, our data show a novel multikinase modulator that might be therapeutically effective in BCR-ABL1-STAT5-related malignancies.en_US
dc.languageengen_US
dc.relationDesarrollo Preclínico de Nuevas Estructuras Bioactivas Moduladoras de Las Actividades Oncogénicas de Stat3/5 O de Los Receptores de Estrógenosen_US
dc.relationDesarrollo Preclínico de Nuevas Estructuras Bioactivas Moduladoras de Las Actividades Oncogénicas de Stat3/5 O de Los Receptores de Estrógenosen_US
dc.relation.ispartofFrontiers in Pharmacologyen_US
dc.sourceFrontiers In Pharmacology [ISSN 1663-9812], v. 9, (Enero 2019)en_US
dc.subject320101 Oncologíaen_US
dc.subject3209 Farmacologíaen_US
dc.subject.otherBcr-Abl1en_US
dc.subject.otherCoumarinen_US
dc.subject.otherDrug Resistanceen_US
dc.subject.otherImatiniben_US
dc.subject.otherLeukemiaen_US
dc.subject.otherNaphthoquinoneen_US
dc.titleA novel naphthoquinone-coumarin hybrid that inhibits BCR-ABL1-STAT5 oncogenic pathway and reduces survival in imatinib-resistant chronic myelogenous leukemia cellsen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fphar.2018.01546en_US
dc.identifier.scopus85061906383-
dc.identifier.isi000455319100001-
dc.contributor.authorscopusid36604772400-
dc.contributor.authorscopusid7006442271-
dc.contributor.authorscopusid35324307900-
dc.contributor.authorscopusid57206731335-
dc.contributor.authorscopusid6701492347-
dc.contributor.authorscopusid8681043500-
dc.contributor.authorscopusid7003810011-
dc.contributor.authorscopusid7003603506-
dc.contributor.authorscopusid14024036100-
dc.contributor.authorscopusid6701825073-
dc.contributor.authorscopusid6506777525-
dc.identifier.issueJAN-
dc.relation.volume9en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.contributor.daisngid3922169-
dc.contributor.daisngid909211-
dc.contributor.daisngid4981952-
dc.contributor.daisngid13167518-
dc.contributor.daisngid749099-
dc.contributor.daisngid128315-
dc.contributor.daisngid384944-
dc.contributor.daisngid1724161-
dc.contributor.daisngid3211275-
dc.contributor.daisngid425077-
dc.contributor.daisngid795544-
dc.description.numberofpages17en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:Martin-Rodriguez, P-
dc.contributor.wosstandardWOS:Guerra, B-
dc.contributor.wosstandardWOS:Hueso-Falcon, I-
dc.contributor.wosstandardWOS:Aranda-Tavio, H-
dc.contributor.wosstandardWOS:Diaz-Chico, J-
dc.contributor.wosstandardWOS:Quintana, J-
dc.contributor.wosstandardWOS:Estevez, F-
dc.contributor.wosstandardWOS:Diaz-Chico, B-
dc.contributor.wosstandardWOS:Amesty, A-
dc.contributor.wosstandardWOS:Estevez-Braun, A-
dc.contributor.wosstandardWOS:Fernandez-Perez, L-
dc.date.coverdateEnero 2019en_US
dc.identifier.ulpgcen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.sjr1,228
dc.description.jcr4,225
dc.description.sjrqQ1
dc.description.jcrqQ1
item.grantfulltextopen-
item.fulltextCon texto completo-
crisitem.author.deptFarmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptFarmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptFarmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.orcid0000-0002-2378-3242-
crisitem.author.orcid0000-0003-4355-5682-
crisitem.author.orcid0000-0002-0559-9097-
crisitem.author.orcid0000-0002-0944-990X-
crisitem.author.orcid0000-0001-8225-4538-
crisitem.author.orcid0000-0002-9728-2774-
crisitem.author.orcid0000-0001-7802-465X-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameMartín Rodríguez, Patricia-
crisitem.author.fullNameGuerra Hernández, Carlos Borja-
crisitem.author.fullNameAranda Tavío, Haidee Magdalena-
crisitem.author.fullNameDíaz Chico, Juan Carlos-
crisitem.author.fullNameQuintana Aguiar, José Martín-
crisitem.author.fullNameEstévez Rosas, Francisco Jesús-
crisitem.author.fullNameDíaz Chico, Bonifacio-
crisitem.author.fullNameFernández Pérez, Leandro Fco-
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