Turkish Neurosurgery 2020 , Vol 30 , Num 6
Ellagic Acid Enhances Antitumor Efficacy of Temozolomide in an in vitro Glioblastoma Model
Abdurrahman CETIN1,Burcu BILTEKIN2
1Health Sciences University, Gazi Yasargil Education and Research Hospital, Department of Neurosurgery, Diyarbakir, Turkey
2Istanbul University, Cerrahpasa Faculty of Medicine, Department of Histology and Embryology, Cerrahpasa, Istanbul, Turkey
DOI : 10.5137/1019-5149.JTN.26026-19.1 AIM: To observe the effect of combining ellagic acid (EA), a natural phenol present in fruits and vegetables, and temozolomide (TMZ) on the proliferation and expression profile of C6 glioma cell line.

MATERIAL and METHODS: Rat C6 glioma cells were treated with 100-?M EA combined with 100 ?M TMZ for 24, 48, and 72 hours (h). Cell proliferation and p53 and caspase-3 protein levels were evaluated using immunocytochemistry. Multi drug resistance 1 (MDR1), O6-methylguanine-DNA methyltransferase (MGMT), and apoptotic protein (caspase-3 and p53) expressions were assessed using reverse transcription polymerase chain reaction (RT-PCR).

RESULTS: EA combined with TMZ conspicuously reduced the cell viability at all incubation times (p<0.001). EA significantly downregulated MGMT expression regardless of the presence of TMZ even at early hours (p<0.001). The combination therapy reduced MDR1 expression only on 48 h in comparison with TMZ alone. EA alone upregulated caspase-3 at 48 h but upregulated p53 at 48 and 72 h. The combined therapy enhanced the immunoreactivities of p53 and caspase-3 proteins independent of the treatment durations but not of the genes.

CONCLUSION: EA combined with TMZ may have a potential antiproliferative efficacy by inhibiting MGMT expression and activating apoptotic protein, p53 and caspase-3, expression. Keywords : Ellagic acid, Temozolomide, Glioma, MGMT, C6 glioma

Corresponding author : Abdurrahman CETIN, acetin2147@gmail.com