The antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma

dc.contributor.authorGüven, Mustafa
dc.contributor.authorTaşpınar, Filiz
dc.contributor.authorDenizler-Ebiri, Farika Nur
dc.contributor.authorCastresana, Javier S
dc.contributor.authorTaşpınar, Mehmet
dc.date.accessioned2023-09-29T06:28:10Z
dc.date.available2023-09-29T06:28:10Z
dc.date.issued2023
dc.departmentTıp Fakültesi
dc.description.abstractGlioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.
dc.identifier.doi10.1007/s12032-023-02079-6
dc.identifier.issn1357-0560
dc.identifier.issue8en_US
dc.identifier.pmid37403006
dc.identifier.scopusqualityQ2
dc.identifier.urihttps:/dx.doi.org10.1007/s12032-023-02079-6
dc.identifier.urihttps://hdl.handle.net/20.500.12451/11008
dc.identifier.volume40en_US
dc.identifier.wosWOS:001022961600001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMedical Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectDNA Repair
dc.subjectGlioblastoma
dc.subjectTemozolomide
dc.subjectTrichostatin A
dc.titleThe antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma
dc.typeArticle

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