Show simple item record

dc.contributor.authorBuociková, Verona
dc.contributor.authorLonghin, Eleonora Marta
dc.contributor.authorPilalis, Eleftherios
dc.contributor.authorMastrokalou, Chara
dc.contributor.authorMiklíková, Svetlana
dc.contributor.authorCihova, Marina
dc.contributor.authorPoturnayova, Alexandra
dc.contributor.authorMackova, Katarina
dc.contributor.authorBábelová, Andrea
dc.contributor.authorTrnkova, Lenka
dc.contributor.authorEl Yamani, Naouale
dc.contributor.authorZheng, Congying
dc.contributor.authorRios-Mondragon, Ivan
dc.contributor.authorLabudova, Martina
dc.contributor.authorCsaderova, Lucia
dc.contributor.authorKuracinova, Kristina Mikus
dc.contributor.authorMakovicky, Peter
dc.contributor.authorKučerová, Lucia
dc.contributor.authorMatuskova, Miroslava
dc.contributor.authorCimpan, Mihaela-Roxana
dc.contributor.authorDusinska, Maria
dc.contributor.authorBabal, Pavel
dc.contributor.authorChatziioannou, Aristotelis
dc.contributor.authorGábelová, Alena
dc.contributor.authorRundén-Pran, Elise
dc.contributor.authorSmolkova, Bozena
dc.date.accessioned2022-02-09T08:50:04Z
dc.date.available2022-02-09T08:50:04Z
dc.date.created2022-02-02T12:37:49Z
dc.date.issued2022
dc.identifier.citationBiomedicine and Pharmacotherapy. 2022, 147, 112662.en_US
dc.identifier.issn0753-3322
dc.identifier.urihttps://hdl.handle.net/11250/2977894
dc.description.abstractAcquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.en_US
dc.language.isoengen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleDecitabine potentiates efficacy of doxorubicin in a preclinical trastuzumab-resistant HER2-positive breast cancer modelsen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.rights.holder© 2022 The Authors. Published by Elsevier Masson SAS.en_US
dc.source.pagenumber14en_US
dc.source.volume147en_US
dc.source.journalBiomedicine and Pharmacotherapyen_US
dc.identifier.doi10.1016/j.biopha.2022.112662
dc.identifier.cristin1996908
dc.relation.projectNorges forskningsråd: 271075en_US
dc.relation.projectNorges forskningsråd: 288768en_US
dc.source.articlenumber112662en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal