title: Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression.
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.
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.affiliation: Department of Neurosurgery, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bekar
authors.affiliation: Department of Microbiology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Ferah
authors.initials: F
authors.lastname: Budak
authors.affiliation: Department of Chemistry, Science Faculty, Uludag University Bursa, Turkey.
authors.forename: Saliha
authors.initials: S
authors.lastname: Sahin
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.affiliation: Department of Neurosurgery, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Mevlut Ozgur
authors.initials: MO
authors.lastname: Taskapılıoglu
authors.affiliation: Department of Neurosurgery, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Kocaeli
authors.affiliation: Department of Pathology, Medical Faculty, Uludag University Bursa, Turkey.
authors.forename: Sahsine
authors.initials: S
authors.lastname: Tolunay
authors.affiliation: Department of Biology, Science Faculty, Uludag University Bursa, Turkey.
authors.forename: Hulusi
authors.initials: H
authors.lastname: Malyer
authors.affiliation: Department of Chemistry, Science Faculty, Uludag University Bursa, Turkey.
authors.forename: Cevdet
authors.initials: C
authors.lastname: Demir
authors.affiliation: Department of Biology, Science Faculty, Balikesir University Balikesir, Turkey.
authors.forename: Gulendam
authors.initials: G
authors.lastname: Tumen
keywords: MicroRNA; Olea europaea leaf extract; cancer stem cell; glioblastoma multiforme; temozolomide