Olea Europaea Leaf Extract Attenuates Temozolomide-induced Senescence-associated Secretion Phenotype in Glioblastoma

Erçelik M., Tunca B., Aksoy S., Tekin Ç., Tezcan G.

TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES, vol.20, no.2, pp.68-77, 2023 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 2
  • Publication Date: 2023
  • Doi Number: 10.4274/tjps.galenos.2022.57639
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, CAB Abstracts, International Pharmaceutical Abstracts, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.68-77
  • Bursa Uludag University Affiliated: Yes


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<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-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<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.