Olea europaea leaf extract alters microRNA expression in human glioblastoma cells.
OBJECTIVE
Glioblastoma multiforme (GBM) is the most common and the most lethal form of primary malignant tumors in the central nervous system. There is an increasing need for the development of more efficient therapeutic approaches for the treatment of these patients. One of the most attractive cancer therapy methods to date is the induction of tumor cell death by certain phytochemicals. Interestingly, bioactive compounds have been shown to alter micro RNA (miRNA) expression involved in several biological processes at the posttranscriptional level. The present study aimed to evaluate whether Olea europaea leaf extract (OLE) has an anticancer effect and modulates miRNA expression in GBM.


METHODS
Firstly, the anti-proliferative activity of OLE and the nature of the interaction with temozolomide (TMZ) of OLE were tested in human glioblastoma cell line T98G cells by trypan blue and WST-1 assays and than realized miRNA PCR array analysis. Potential mRNA targets were analyzed bioinformatically.


RESULTS
OLE exhibited anti-proliferative effects on T98G cell lines. Cells were treated with temozolomide (TMZ) in the presence OLE, and changes to miRNA expression levels were identified by PCR array analysis. miRNA target genes are involved in cell cycle and apoptotic pathways. Specifically, miR-181b, miR-153, miR-145, miR-137, and let-7d were significantly upregulated after treatment with both TMZ and OLE.


CONCLUSIONS
Our results suggest that OLE modulates the expression of some miRNAs related to anticancer activity in GBM and the response to TMZ. Further studies and validations are needed, but we suggest that OLE might be used for in vivo studies and future medical drug studies.
Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey. btunca@uludag.edu.tr
Berrin
B
Tunca
Gulcin
G
Tezcan
Gulsah
G
Cecener
Unal
U
Egeli
Secil
S
Ak
Hulusi
H
Malyer
Gulendam
G
Tumen
Ayhan
A
Bilir
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D031658:Olea / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; C545567:MIRN137 microRNA, human; C541010:MIRN145 microRNA, human; C556500:MIRN153 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D010936:Plant Extracts; C487931:mirnlet7 microRNA, human; D003606:Dacarbazine; D000077204:Temozolomide