1. Olea europaea Leaf Extract Improves the Efficacy of Temozolomide Therapy by Inducing MGMT Methylation and Reducing P53 Expression in Glioblastoma
- Author
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Ahmet Bekar, Mevlut Ozgur Taskapilioglu, Unal Egeli, Hasan Kocaeli, Gulcin Tezcan, Hilal Demirci, Ozgur Vatan, Gulsah Cecener, Sahsine Tolunay, Berrin Tunca, Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirürji Anabilim Dalı., Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü., Tezcan, Gülçin, Tunca, Berrin, Demirci, Hilal, Bekar, Ahmet, Taşkapılıoğlu, Mevlut Özgür, Kocaeli, Hasan, Egeli, Ünal, Çeçener, Gülşah, Tolunay, Şahsine, Vatan, Özgür, AAP-9988-2020, AAH-3843-2020, AAI-1612-2021, AAW-5254-2020, ABI-6078-2020, AAH-1420-2021, ABB-8161-2020, and O-7508-2015
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Unclassified drug ,MGMT protein, human ,DNA methyltransferase ,Medicine (miscellaneous) ,Mitosis inhibition ,IC50 ,TP53 protein, human ,Repair gene mgmt ,Protein methylation ,Western blotting ,0-6-methylguanine-dna methyltransferase ,CpG islands ,Promoter regions, genetic ,0302 clinical medicine ,Glioblastoma ,DNA Alkyltransferase ,Temozolomide ,Olea europaea leaf extract ,Mechanisms ,Gliomas ,Hypermethylation ,Middle aged ,Cytotoxicity ,Protein p53 ,DNA strand breakage ,Analogs and derivatives ,Tumor ,DNA methylation ,Nutrition and Dietetics ,medicine.diagnostic_test ,Promoter region ,Plant leaf ,Methylated DNA protein cysteine methyltransferase ,Polymerase chain reaction ,Dacarbazine ,Plant extract ,Chemistry ,Real-time polymerase chain reaction ,Antineoplastic agent ,Oncology ,CpG site ,Biochemistry ,Inhibitory concentration 50 ,DNA ligase ,030220 oncology & carcinogenesis ,Antitumor drug temozolomide ,Dose-response relationship, drug ,Female ,Lnactivation ,Human ,medicine.drug ,Adult ,Cells ,Tumor suppressor protein p53 ,Drug potentiation ,Biology ,WST-1 assay ,Article ,03 medical and health sciences ,Western blot ,Drug resistance, neoplasm ,Cell Line, Tumor ,Olea ,Dose response ,microRNA ,Genetics ,medicine ,Chemotherapy ,Humans ,Nutrition & dietetics ,Comet assay ,Aged ,Antineoplastic activity ,Dna ,Plant extracts ,Tumor cell line ,Tumor suppressor protein ,Metabolism ,030104 developmental biology ,DNA repair enzymes ,Tumor suppressor proteins ,Human cell ,Drug resistance ,CpG island ,Cancer research ,DNA damage ,Protein expression ,Cell line ,DNA modification methylases ,Olive tree ,Plant leaves - Abstract
Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 mu M TMZ plus 1mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1mg/mL OLE plus 350 mu M TMZ on the formation of DNA strand breaks was significantly higher than that of 450 mu M TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.
- Published
- 2017
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