• Abdurrahman Çetin, Burcu Biltekin, and Sevgin Degirmencioglu.
• Department of Neurosurgery, Gazi Yaşargil Education and Research Hospital of Health Science University, Diyarbakır, Turkey. Electronic address: acetin2147@gmail.com.
• World Neurosurg. 2019 Dec 1; 132: e59-e65.

BackgroundThe anticarcinogenic effect of ellagic acid (EA), a natural phenol of fruits and vegetables, has been investigated in several types of tumors. The combined effect of EA with bevacizumab (BEV), a common drug used in treatment of recurrent glioma, on glioblastoma has not been reported. This study observed the combined effect of EA with BEV on the expression profile of the C6 glioma cell line.MethodsRat C6 glioma cells were treated with EA at 100 μmol/L concentration in combination with BEV at 100 ng/mL concentration for 24, 48, and 72 hours. Cell proliferation was detected by 5-bromo-2'-deoxyuridine immunohistochemistry, and p53 and caspase-3 protein levels were determined by immunohistochemistry and assessed by the H-Score. Expression profiles for P-glycoprotein (MDR1), O6-methylguanine DNA methyltransferase (MGMT), caspase-3, and p53 related proteins were detected by reverse transcriptase polymerase chain reaction after EA treatment with or without BEV.ResultsEA combined with BEV conspicuously reduced the cell viability of C6 glioma cells for all incubation times. EA significantly downregulated expression of MGMT regardless of combination with BEV even in the early hours after treatment. Combined EA and BEV reduced MDR1 expression only at 72 hours. EA affected the apoptotic proteins of p53 and caspase-3 at protein level in a time-dependent manner, but not at gene level.ConclusionsThis study suggests successful antiproliferative efficacy of EA combined with BEV, probably through inhibition of MGMT expression and time-dependent inhibition of MDR1. EA combined with BEV may be an alternative treatment for drug-resistant gliomas.Copyright © 2019 Elsevier Inc. All rights reserved.

32 keywords...

hide…