Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression
Gulcin Tezcan1, Berrin Tunca1, Ahmet Bekar2
1Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
Abstract:
The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.
Insights
Olea europaea leaf extract (OLE) shows anticancer effects against glioblastoma multiforme (GBM) cells by inducing cell death and modulating miRNA expression. OLE combined with temozolomide (TMZ) synergistically enhances these effects, suggesting potential for GBM therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) stem-like cells (GSCs) drive tumor recurrence and drug resistance.
- Identifying novel therapeutic strategies targeting GSCs is crucial for improving GBM treatment outcomes.
Purpose of the Study:
- To evaluate the anticancer effects of Olea europaea leaf extract (OLE) on GBM cell lines.
- To investigate the synergistic effect of OLE in combination with temozolomide (TMZ) on GSCs.
- To elucidate the molecular mechanisms, including miRNA expression, underlying OLE's effects in GBM.
Main Methods:
- Anti-proliferative activity assessed using WST-1 assay in GBM cell lines (T98G, U-138MG, U-87MG).
- Apoptosis and necrosis analyzed via Annexin V/FITC and TUNEL assays.
- miRNA and mRNA expression profiling in GSCs performed using RT-qPCR.
Main Results:
- OLE demonstrated significant anti-proliferative effects on GBM cell lines through apoptosis and necrosis.
- OLE treatment upregulated miR-153, miR-145, and miR-137 expression while downregulating their target genes in GSCs.
- The combination of OLE and TMZ exhibited synergistic cell death induction in GBM cells.
Conclusions:
- OLE exhibits anticancer properties against GBM, impacting cell death pathways and miRNA expression.
- OLE, particularly in combination with TMZ, shows promise in targeting GBM stem-like cells.
- OLE's modulation of miRNA expression suggests a novel mechanism for interfering with GSC pluripotency, warranting further investigation for GBM therapeutics.
