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Tezcan G, Tunca B, Bekar A, et al. Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression. Am J Cancer Res. 2014;4(5):572-90
Tezcan, G., Tunca, B., Bekar, A., Budak, F., Sahin, S., Cecener, G., Egeli, U., Taskapılıoglu, M. O., Kocaeli, H., Tolunay, S., Malyer, H., Demir, C., & Tumen, G. (2014). Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression. American journal of cancer research, 4(5), 572-90.
Tezcan, Gulcin, et al. "Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression." American journal of cancer research vol. 4,5 (2014): 572-90.
Tezcan G, Tunca B, Bekar A, Budak F, Sahin S, Cecener G, Egeli U, Taskapılıoglu MO, Kocaeli H, Tolunay S, Malyer H, Demir C, Tumen G. Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression. Am J Cancer Res. 2014 Sep 06;4(5):572-90. eCollection 2014. PMID: 25232498; PMCID: PMC4163621.
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Am J Cancer Res. 2014 Sep 06;4(5):572-90. eCollection 2014.

Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression.

American journal of cancer research

Gulcin Tezcan, Berrin Tunca, Ahmet Bekar, Ferah Budak, Saliha Sahin, Gulsah Cecener, Unal Egeli, Mevlut Ozgur Taskapılıoglu, Hasan Kocaeli, Sahsine Tolunay, Hulusi Malyer, Cevdet Demir, Gulendam Tumen

Affiliations

  1. Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
  2. Department of Neurosurgery, Medical Faculty, Uludag University Bursa, Turkey.
  3. Department of Microbiology, Medical Faculty, Uludag University Bursa, Turkey.
  4. Department of Chemistry, Science Faculty, Uludag University Bursa, Turkey.
  5. Department of Pathology, Medical Faculty, Uludag University Bursa, Turkey.
  6. Department of Biology, Science Faculty, Uludag University Bursa, Turkey.
  7. Department of Biology, Science Faculty, Balikesir University Balikesir, Turkey.

PMID: 25232498 PMCID: PMC4163621

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.

Keywords: MicroRNA; Olea europaea leaf extract; cancer stem cell; glioblastoma multiforme; temozolomide

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