期刊论文详细信息
Turkish Journal of Pharmaceutical Sciences
Olea europaea L. Leaf Extract Attenuates Temozolomide-Induced Senescence-Associated Secretion Phenotype in Glioblastoma
article
Melis ERÇELİK1  Berrin TUNCA1  Seçil AK AKSOY2  Çağla AK AKSOY1  Gülçin TEZCAN3 
[1] Bursa Uludağ University, Faculty of Medicine, Department of Medical Biology;Bursa Uludağ University, İnegol Vocation School;Bursa Uludağ University, Faculty of Dentistry, Department of Fundamental Sciences
关键词: Glioblastoma;    Olea europaea leaf extract;    temozolomide;    senescence;    SASP;   
DOI  :  10.4274/tjps.galenos.2022.57639
来源: Galenos Yayinevi
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【 摘 要 】

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 β-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-κB1) 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<0.001). Besides, OLE + TMZ reduced the proportion of senescent cells (p<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-κB1, 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<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.

【 授权许可】

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