Inhibition of O6-methylguanine-DNA-methyltransferase (MGMT) by lomeguatrib reduces multiple myeloma cell viability and impairs DNA repair in MGMT-proficient cells

Basit Öğe Kaydı
dc.authoridCetintav, Bekir/0000-0001-7251-1211
dc.authoridSUNGUROGLU, ASUMAN/0000-0001-7693-0958
dc.authoridBeksac, Meral/0000-0003-1797-8657
dc.authoridAKCORA YILDIZ, Dilara/0000-0003-2586-4385
dc.authorwosidCetintav, Bekir/AAE-9930-2019
dc.authorwosidSUNGUROGLU, ASUMAN/AAQ-4882-2020
dc.authorwosidBeksac, Meral/D-6411-2013
dc.contributor.authorAkcora-Yildiz, Dilara
dc.contributor.authorOzkan, Tulin
dc.contributor.authorCetintav, Bekir
dc.contributor.authorYukselten, Yunus
dc.contributor.authorCalis, Seyma
dc.contributor.authorSevim-Nalkiran, Hatice
dc.contributor.authorTurkel, Nezaket
dc.date.accessioned2024-05-19T14:40:56Z
dc.date.available2024-05-19T14:40:56Z
dc.date.issued2024
dc.departmentİstinye Üniversitesien_US
dc.description.abstractThe function of direct DNA damage repair protein, namely MGMT in MM, and the impact of MGMT on melphalan treatment remains unclear. We showed a significantly higher MGMT mRNA expression in CD138+ myeloma cells than in matched CD138-nontumorigenic cells derived from newly diagnosed and relapsed/refractory MM patients using qPCR. However, using gene expression databases, a similar expression of MGMT was observed during disease progression. MGMT depletion by its specific inhibitor lomeguatrib reduced myeloma cell viability, impaired S phase entry and DNA repair, and increased DNA damage and apoptosis. Apoptosis and DNA damage were further elevated by combined treatment with lomeguatrib and melphalan in RPMI 8226 cells. This is the first study demonstrating MGMT inhibition enhances DNA damage-induced apoptosis and melphalan cytotoxicity in MGMT-proficient MM cells and suggesting using lomeguatrib might have clinical importance in treating MM and overcoming melphalan resistance in MGMT-proficient patients.en_US
dc.description.sponsorshipTrkiye Bilimsel ve Teknolojik Arascedil;timath;rma Kurumu [113Z383, 04-176-13]; Scientific and Technological Research Council of Turkey (TUBITAK)en_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK, grant no. 113Z383). The experiments with human cells were approved by the Ethics Committee of Ankara University School of Medicine (Protocol 04-176-13). All MM patients and healthy volunteers were informed about the purpose of the study, and written consent was obtained from each participant in accordance with the Declaration of Helsinki.en_US
dc.identifier.doi10.1111/cbdd.14465
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.issue2en_US
dc.identifier.urihttps://doi.org10.1111/cbdd.14465
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5039
dc.identifier.volume103en_US
dc.identifier.wosWOS:001153172200001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofChemical Biology & Drug Designen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240519_kaen_US
dc.subjectDna Repairen_US
dc.subjectLomeguatriben_US
dc.subjectMelphalanen_US
dc.subjectMgmten_US
dc.subjectMultiple Myelomaen_US
dc.titleInhibition of O6-methylguanine-DNA-methyltransferase (MGMT) by lomeguatrib reduces multiple myeloma cell viability and impairs DNA repair in MGMT-proficient cellsen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu