Synthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast cancer

dc.contributor.authorEskiler, Gamze Güney
dc.contributor.buuauthorÇeçener, Gülşah
dc.contributor.buuauthorEgeli, Ünal
dc.contributor.buuauthorTunca, Berrin
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0002-3820-424Xtr_TR
dc.contributor.orcid0000-0001-7904-883Xtr_TR
dc.contributor.orcid0000-0002-1619-6680tr_TR
dc.contributor.researcheridAAP-9988-2020tr_TR
dc.contributor.researcheridAAH-1420-2021tr_TR
dc.contributor.researcheridABI-6078-2020tr_TR
dc.contributor.scopusid6508156530tr_TR
dc.contributor.scopusid55665145000tr_TR
dc.contributor.scopusid6602965754tr_TR
dc.date.accessioned2022-12-28T12:35:34Z
dc.date.available2022-12-28T12:35:34Z
dc.date.issued2018-11-15
dc.description.abstractPurpose The purpose of the study was to produce BMN 673 loaded solid lipid nanoparticles (SLNs) to improve its therapeutic index, to minimize toxicity and to overcome homologous recombination (HR)-mediated resistance.MethodsFirstly, BMN 673-SLNs were characterized using Nano Zeta Sizer. After treatment with different concentrations of BMN 673 and BMN 673-SLNs, cell viability of HCC1937((BRCA1-/-)), HCC1937-R (BMN 673-resistant) TNBC and MCF-10A normal human mammary breast epithelial cell line was analyzed by WST-1 assay. In an attempt to assess the therapeutic synthetic lethality efficacy of SLNs formulation, cell cycle arrest, DNA damage, mRNA expression levels of PARP1, H2AFX, RAD51 and BRCA1 gene were investigated. Then, PARP, ?H2AX, RAD51 and BRCA1 protein expression and nuclear localization were analyzed by western blot and immunofluorescence analysis.ResultsWhen compared with BMN 673, BMN 673-SLNs showed remarkably a decrease in HCC1937 and HCC1937-R cells with less damage to MCF-10A cells. BMN 673-SLNs significantly induced toxicity through double-stranded DNA breaks, G2/M cell cycle arrest and PARP cleavage in TNBC cells. Additionally, BMN 673-resistance was mediated by miR-107, miR-193b and miR-1255b targeting BRCA1 and RAD51 in HCC1937 and HCC1937-R cells. However, BMN 673-SLNs treatment could overcome HR-mediated resistance in TNBC cells.Conclusions As a result, our findings suggest that SLNs formulation strongly provides a synthetic lethal therapeutic potential in BRCA1 mutated sensitive and resistant TNBC cells.en_US
dc.identifier.citationEskiler, G. G. vd. (2018). ''Synthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast cancer''. Pharmaceutical Research, 35(11).en_US
dc.identifier.issn0724-8741
dc.identifier.issn1573-904X
dc.identifier.issue11tr_TR
dc.identifier.pubmed30255456tr_TR
dc.identifier.scopus2-s2.0-85053843953tr_TR
dc.identifier.urihttps://doi.org/10.1007/s11095-018-2502-6
dc.identifier.urilink.springer.com/article/10.1007/s11095-018-2502-6
dc.identifier.urihttp://hdl.handle.net/11452/30141
dc.identifier.volume35tr_TR
dc.identifier.wos000445655600004tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.bapBUAP(T)-2015/1tr_TR
dc.relation.collaborationYurt içitr_TR
dc.relation.journalPharmaceutical Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectChemistryen_US
dc.subjectPharmacology & pharmacyen_US
dc.subjectBMN 673 (Talozoparib)en_US
dc.subjectPoly ADP ribose polymerase (PARP) inhibitorsen_US
dc.subjectSolid lipid nanoparticles (SLNs)en_US
dc.subjectSynthetic lethalityen_US
dc.subjectTriple negative breast cancer (TNBC)en_US
dc.subjectPoly(ADP-ribose) polymerase-1/2 inhibitoren_US
dc.subjectParp inhibitoren_US
dc.subjectDNA-repairen_US
dc.subjectVivo sensitivityen_US
dc.subjectHighly polenten_US
dc.subjectIn-vitroen_US
dc.subjectResistanceen_US
dc.subjectDeficienten_US
dc.subjectMutationsen_US
dc.subjectTherapyen_US
dc.subject.emtreeBRCA1 proteinen_US
dc.subject.emtreeHistone H2AXen_US
dc.subject.emtreeNicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferaseen_US
dc.subject.emtreeNicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1en_US
dc.subject.emtreeNicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitoren_US
dc.subject.emtreeRad51 proteinen_US
dc.subject.emtreeSolid lipid nanoparticleen_US
dc.subject.emtreeTalazopariben_US
dc.subject.emtreeAntineoplastic agenten_US
dc.subject.emtreeBRCA1 proteinen_US
dc.subject.emtreeBRCA1 protein, humanen_US
dc.subject.emtreeDrug carrieren_US
dc.subject.emtreeLipiden_US
dc.subject.emtreeNanoparticleen_US
dc.subject.emtreeNicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitoren_US
dc.subject.emtreePhthalazine derivativeen_US
dc.subject.emtreeTalazopariben_US
dc.subject.emtreeAntineoplastic activityen_US
dc.subject.emtreeApoptosisen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeCell cycle arresten_US
dc.subject.emtreeCell cycle M phaseen_US
dc.subject.emtreeCell populationen_US
dc.subject.emtreeCell viabilityen_US
dc.subject.emtreeCytotoxicityen_US
dc.subject.emtreeDispersityen_US
dc.subject.emtreeDNA damageen_US
dc.subject.emtreeDouble stranded DNA breaken_US
dc.subject.emtreeG2 phase cell cycle checkpointen_US
dc.subject.emtreeGene controlen_US
dc.subject.emtreeGene expressionen_US
dc.subject.emtreeGene mutationen_US
dc.subject.emtreeHCC1937 cell lineen_US
dc.subject.emtreeHCC1937-R cell lineen_US
dc.subject.emtreeHomologous recombinationen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeHuman cellen_US
dc.subject.emtreeImmunofluorescenceen_US
dc.subject.emtreeImmunofluorescence microscopyen_US
dc.subject.emtreeIn vitro studyen_US
dc.subject.emtreeLoading drug doseen_US
dc.subject.emtreeMCF-10A cell lineen_US
dc.subject.emtreeMRNA expression levelen_US
dc.subject.emtreeParticle sizeen_US
dc.subject.emtreePolymerase chain reactionen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeProtein expressionen_US
dc.subject.emtreeReverse transcription polymerase chain reactionen_US
dc.subject.emtreeTherapeutic indexen_US
dc.subject.emtreeTherapyen_US
dc.subject.emtreeWestern blottingen_US
dc.subject.emtreeWST-1 assayen_US
dc.subject.emtreeZeta potentialen_US
dc.subject.emtreeCell cycle checkpointen_US
dc.subject.emtreeChemistryen_US
dc.subject.emtreeDrug effecten_US
dc.subject.emtreeGeneticsen_US
dc.subject.emtreeMutationen_US
dc.subject.emtreeTriple negative breast canceren_US
dc.subject.emtreeTumor cell lineen_US
dc.subject.meshAntineoplastic agentsen_US
dc.subject.meshBRCA1 proteinen_US
dc.subject.meshCell cycle checkpointsen_US
dc.subject.meshCell line, tumoren_US
dc.subject.meshDNA breaks, double-strandeden_US
dc.subject.meshDrug carriersen_US
dc.subject.meshHumansen_US
dc.subject.meshLipidsen_US
dc.subject.meshMutationen_US
dc.subject.meshNanoparticlesen_US
dc.subject.meshPhthalazinesen_US
dc.subject.meshPoly(ADP-ribose) polymerase inhibitorsen_US
dc.subject.meshTriple negative breast neoplasmsen_US
dc.subject.scopusOlaparib; Ovarian Neoplasms; Homologous Recombinationen_US
dc.subject.wosChemistry, multidisciplinaryen_US
dc.subject.wosPharmacology & pharmacyen_US
dc.titleSynthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast canceren_US
dc.typeArticle
dc.wos.quartileQ1 (Pharmacology & pharmacy)en_US
dc.wos.quartileQ2 (Chemistry, multidisciplinary)en_US

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