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<i>Olea</i><i> europaea</i> L. Leaf Extract Attenuates Temozolomide-Induced Senescence-Associated Secretion Phenotype in Glioblastoma

Ercelik, Melis; Tunca, Berrin; Ak Aksoy, Secil; Tekin, Cagla; Tezcan, Gulcin


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    <subfield code="a">&lt;i&gt;Olea&lt;/i&gt;&lt;i&gt; europaea&lt;/i&gt; L. Leaf Extract Attenuates Temozolomide-Induced Senescence-Associated Secretion Phenotype in Glioblastoma</subfield>
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    <subfield code="a">&lt;p&gt;Objectives: The purpose of this study was to investigate the effect of Olea europaea L. leaf extract (OLE) on senescence and senescence-associated secretory phenotype (SASP) caused by temozolomide (TMZ) in glioblastoma (GB).Materials and Methods: A senescence beta-galactosidase assay and a colony formation assay were used to determine the effects of OLE, TMZ, and OLE + TMZ on the cellular senescence and aggressiveness of GB cell lines T98G and U87MG. mRNA expression levels of p53, a senescence factor, interleukin (IL)-6, matrix metalloproteinases (MMP)-9, and nuclear factor kappa B1 (NF-kappa B1) as SASP factors and Bcl-2 and Bax as senolytic markers were assessed using quantitative reverse transcription-real-time polymerase chain reaction. Cells were double-stained with acridine orange and propidium iodide to observe the cell morphology.Results: TMZ increased the senescence rate of GB cells (p&amp;lt;0.001). Besides, OLE + TMZ reduced the proportion of senescent cells (p&amp;lt;0.001) and their capability to form colonies compared to TMZ-only-treated cells. Additionally, OLE + TMZ co-treatment elevated the mRNA expression levels of MMP-9, IL-6, NF-kappa B1, p53, and the Bax/Bcl-2 ratio compared to TMZ-only treatment. Especially in U87MG cells, involvement of OLE in TMZ treatments increased more than six times in the Bax/Bcl-2 ratio compared to TMZ-only, which induced the apoptosis-like morphological features (p&amp;lt;0.0001).Conclusion: Collectively, our findings presented the inhibitory effect of OLE on TMZ-mediated SASP-factor production in GB and, accordingly, its potential contribution to elongate the time of recurrence.&lt;/p&gt;</subfield>
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