Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages

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dc.contributor.authorKarabay, Arzu Zeynep
dc.contributor.authorÖzkan, Tülin
dc.contributor.authorKoç, Aslı
dc.contributor.authorHekmatshoar, Yalda
dc.contributor.authorGürkan-Alp, A. Selen
dc.contributor.authorSunguroğlu, Asuman
dc.date.accessioned2023-12-15T13:52:31Z
dc.date.available2023-12-15T13:52:31Z
dc.date.issued2023en_US
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri, Tıbbi Biyoloji Ana Bilim Dalıen_US
dc.description.abstractIn this study, we aimed to analyze the effects of first and second-generation Bcr-Abl tyrosine kinase inhibitors, imatinib and nilotinib on LPS/IFN gamma activated RAW 264.7 macrophages. Our data revealed that imatinib was less effective on nitrite levels and more toxic on macrophages compared to nilotinib. Therefore, we further analysed the effect of nilotinib on various inflammatory markers including iNOS, COX-2, NFkB, IL-6, p-ERK, p-p38 and p-JNK in LPS/IFN gamma activated RAW264.7 macrophages. Spectrophotometric viability test and Griess assay,western blot, RT-PCR and luciferase reporter assays were used to analyze the biological activity of nilotinib. Our findings revealed that nilotinib decreases nitrite levels, iNOS mRNA, iNOS and p-p38 protein expressions significantly whereas induces IL-6 mRNA and p-JNK protein expressions at particular doses. We did not find significant effect of nilotinib on COX-2, p-ERK and nuclear p65 proteins and NFkB transcriptional activity. In addition, the binding mode of nilotinib to iNOS protein was predicted by molecular docking. According to the docking analyses, nilotinib exhibited hydrophobic interactions between MET349, ALA191, VAL346, PHE363, TYR367, MET368, CYS194, TRP366 residues at the binding pocket and the molecule as well as van der Waals interactions at specific residues. In conclusion, our results reveal that, in addition to its anticancer activity, nilotinib can exhibit immune modulatory effects on macrophages through its effects on iNOS, IL-6, p-p38 and p-JNK.en_US
dc.identifier.citationKarabay, A. Z., Özkan, T., Koç, A., Hekmatshoar, Y., Gürkan-Alp, A. S., & Sunguroğlu, A. (2023). Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages. Toxicology in Vitro, 105754.en_US
dc.identifier.issn0887-2333
dc.identifier.issn1879-3177
dc.identifier.scopus2-s2.0-85179939099
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://hdl.handle.net/20.500.12939/4294
dc.identifier.wosWOS:001136967000001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorHekmatshoar, Yalda
dc.language.isoen
dc.relation.ispartofToxicology In Vitro
dc.relation.isversionof10.1016/j.tiv.2023.105754en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectImatiniben_US
dc.subjectMAPKen_US
dc.subjectMacrophageen_US
dc.subjectNilotiniben_US
dc.subjectP-JNKen_US
dc.subjectiNOSen_US
dc.titleNilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages
dc.typeArticle

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