Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

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dc.authorid0000-0002-3052-4556
dc.contributor.authorKaplan, Ozlem
dc.contributor.authorTosun, Nazan Goksen
dc.date.accessioned2026-01-24T12:31:00Z
dc.date.available2026-01-24T12:31:00Z
dc.date.issued2024
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractNeuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBIdot;TAK)
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUB & Idot;TAK). In this study, the facilities of Tokat Gaziosmanpasa University Faculty of Engineering and Architecture Bioengineering Department laboratories were used.
dc.identifier.doi10.1007/s12032-024-02428-z
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue8
dc.identifier.pmid38958814
dc.identifier.scopus2-s2.0-85197384806
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s12032-024-02428-z
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5577
dc.identifier.volume41
dc.identifier.wosWOS:001261578200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherHumana Press Inc
dc.relation.ispartofMedical Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260121
dc.subjectHSP90 inhibition
dc.subjectNeuroblastoma
dc.subjectXL-888
dc.subjectDebio0932
dc.subjectCancer
dc.titleMolecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line
dc.typeArticle

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