Synthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast cancer
dc.contributor.author | Eskiler, Gamze Güney | |
dc.contributor.buuauthor | Çeçener, Gülşah | |
dc.contributor.buuauthor | Egeli, Ünal | |
dc.contributor.buuauthor | Tunca, Berrin | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı. | tr_TR |
dc.contributor.orcid | 0000-0002-3820-424X | tr_TR |
dc.contributor.orcid | 0000-0001-7904-883X | tr_TR |
dc.contributor.orcid | 0000-0002-1619-6680 | tr_TR |
dc.contributor.researcherid | AAP-9988-2020 | tr_TR |
dc.contributor.researcherid | AAH-1420-2021 | tr_TR |
dc.contributor.researcherid | ABI-6078-2020 | tr_TR |
dc.contributor.scopusid | 6508156530 | tr_TR |
dc.contributor.scopusid | 55665145000 | tr_TR |
dc.contributor.scopusid | 6602965754 | tr_TR |
dc.date.accessioned | 2022-12-28T12:35:34Z | |
dc.date.available | 2022-12-28T12:35:34Z | |
dc.date.issued | 2018-11-15 | |
dc.description.abstract | Purpose 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.citation | Eskiler, 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.issn | 0724-8741 | |
dc.identifier.issn | 1573-904X | |
dc.identifier.issue | 11 | tr_TR |
dc.identifier.pubmed | 30255456 | tr_TR |
dc.identifier.scopus | 2-s2.0-85053843953 | tr_TR |
dc.identifier.uri | https://doi.org/10.1007/s11095-018-2502-6 | |
dc.identifier.uri | link.springer.com/article/10.1007/s11095-018-2502-6 | |
dc.identifier.uri | http://hdl.handle.net/11452/30141 | |
dc.identifier.volume | 35 | tr_TR |
dc.identifier.wos | 000445655600004 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Springer | en_US |
dc.relation.bap | BUAP(T)-2015/1 | tr_TR |
dc.relation.collaboration | Yurt içi | tr_TR |
dc.relation.journal | Pharmaceutical Research | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Chemistry | en_US |
dc.subject | Pharmacology & pharmacy | en_US |
dc.subject | BMN 673 (Talozoparib) | en_US |
dc.subject | Poly ADP ribose polymerase (PARP) inhibitors | en_US |
dc.subject | Solid lipid nanoparticles (SLNs) | en_US |
dc.subject | Synthetic lethality | en_US |
dc.subject | Triple negative breast cancer (TNBC) | en_US |
dc.subject | Poly(ADP-ribose) polymerase-1/2 inhibitor | en_US |
dc.subject | Parp inhibitor | en_US |
dc.subject | DNA-repair | en_US |
dc.subject | Vivo sensitivity | en_US |
dc.subject | Highly polent | en_US |
dc.subject | In-vitro | en_US |
dc.subject | Resistance | en_US |
dc.subject | Deficient | en_US |
dc.subject | Mutations | en_US |
dc.subject | Therapy | en_US |
dc.subject.emtree | BRCA1 protein | en_US |
dc.subject.emtree | Histone H2AX | en_US |
dc.subject.emtree | Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase | en_US |
dc.subject.emtree | Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 | en_US |
dc.subject.emtree | Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor | en_US |
dc.subject.emtree | Rad51 protein | en_US |
dc.subject.emtree | Solid lipid nanoparticle | en_US |
dc.subject.emtree | Talazoparib | en_US |
dc.subject.emtree | Antineoplastic agent | en_US |
dc.subject.emtree | BRCA1 protein | en_US |
dc.subject.emtree | BRCA1 protein, human | en_US |
dc.subject.emtree | Drug carrier | en_US |
dc.subject.emtree | Lipid | en_US |
dc.subject.emtree | Nanoparticle | en_US |
dc.subject.emtree | Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor | en_US |
dc.subject.emtree | Phthalazine derivative | en_US |
dc.subject.emtree | Talazoparib | en_US |
dc.subject.emtree | Antineoplastic activity | en_US |
dc.subject.emtree | Apoptosis | en_US |
dc.subject.emtree | Article | en_US |
dc.subject.emtree | Cell cycle arrest | en_US |
dc.subject.emtree | Cell cycle M phase | en_US |
dc.subject.emtree | Cell population | en_US |
dc.subject.emtree | Cell viability | en_US |
dc.subject.emtree | Cytotoxicity | en_US |
dc.subject.emtree | Dispersity | en_US |
dc.subject.emtree | DNA damage | en_US |
dc.subject.emtree | Double stranded DNA break | en_US |
dc.subject.emtree | G2 phase cell cycle checkpoint | en_US |
dc.subject.emtree | Gene control | en_US |
dc.subject.emtree | Gene expression | en_US |
dc.subject.emtree | Gene mutation | en_US |
dc.subject.emtree | HCC1937 cell line | en_US |
dc.subject.emtree | HCC1937-R cell line | en_US |
dc.subject.emtree | Homologous recombination | en_US |
dc.subject.emtree | Human | en_US |
dc.subject.emtree | Human cell | en_US |
dc.subject.emtree | Immunofluorescence | en_US |
dc.subject.emtree | Immunofluorescence microscopy | en_US |
dc.subject.emtree | In vitro study | en_US |
dc.subject.emtree | Loading drug dose | en_US |
dc.subject.emtree | MCF-10A cell line | en_US |
dc.subject.emtree | MRNA expression level | en_US |
dc.subject.emtree | Particle size | en_US |
dc.subject.emtree | Polymerase chain reaction | en_US |
dc.subject.emtree | Priority journal | en_US |
dc.subject.emtree | Protein expression | en_US |
dc.subject.emtree | Reverse transcription polymerase chain reaction | en_US |
dc.subject.emtree | Therapeutic index | en_US |
dc.subject.emtree | Therapy | en_US |
dc.subject.emtree | Western blotting | en_US |
dc.subject.emtree | WST-1 assay | en_US |
dc.subject.emtree | Zeta potential | en_US |
dc.subject.emtree | Cell cycle checkpoint | en_US |
dc.subject.emtree | Chemistry | en_US |
dc.subject.emtree | Drug effect | en_US |
dc.subject.emtree | Genetics | en_US |
dc.subject.emtree | Mutation | en_US |
dc.subject.emtree | Triple negative breast cancer | en_US |
dc.subject.emtree | Tumor cell line | en_US |
dc.subject.mesh | Antineoplastic agents | en_US |
dc.subject.mesh | BRCA1 protein | en_US |
dc.subject.mesh | Cell cycle checkpoints | en_US |
dc.subject.mesh | Cell line, tumor | en_US |
dc.subject.mesh | DNA breaks, double-stranded | en_US |
dc.subject.mesh | Drug carriers | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Lipids | en_US |
dc.subject.mesh | Mutation | en_US |
dc.subject.mesh | Nanoparticles | en_US |
dc.subject.mesh | Phthalazines | en_US |
dc.subject.mesh | Poly(ADP-ribose) polymerase inhibitors | en_US |
dc.subject.mesh | Triple negative breast neoplasms | en_US |
dc.subject.scopus | Olaparib; Ovarian Neoplasms; Homologous Recombination | en_US |
dc.subject.wos | Chemistry, multidisciplinary | en_US |
dc.subject.wos | Pharmacology & pharmacy | en_US |
dc.title | Synthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast cancer | en_US |
dc.type | Article | |
dc.wos.quartile | Q1 (Pharmacology & pharmacy) | en_US |
dc.wos.quartile | Q2 (Chemistry, multidisciplinary) | en_US |
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