• Abdurrahman Çetin and Burcu Biltekin.
• 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: e178-e184.

ObjectiveWe aimed to evaluate the combined effect of ellagic acid (EA) and temozolomide (TEM) on the cadherin switch and angiogenesis in the C6 glioma cell line.MethodsA total of 100 μM EA and 100 μM TEM were applied to rat C6 glioma cells for 24, 48, and 72 hours. Cell proliferation was detected by 5-bromo-2'-deoxyuridine immunohistochemistry. The messenger RNA and protein levels of E-cadherin, N-cadherin, and vascular endothelial growth factor (VEGF) were determined by real-time polymerase chain reaction and their immunohistochemistry, respectively, subsequent to EA treatment combined with TEM.ResultsEA in combination with TEM conspicuously reduced the viability of C6 glioma cells at all incubation times (P < 0.001). EA upregulated the expression of E-cadherin at the gene and protein levels in a time-independent manner (P < 0.05 and P < 0.001, respectively). By the presence of TEM, the increase was exaggerated at 24-hour incubation (P < 0.01). Conversely, EA reduced N-cadherin expression and immunoreactivity in a time-independent manner (P < 0.05 and P < 0.001, respectively), and combination with TEM enhanced this effect at the 24th hour (P < 0.001). Combination also downregulated the gene expression (P < 0.001) and immunoreactivity of VEGF only at 72 hours (P < 0.001).ConclusionsA successful therapeutic efficacy of EA combined with TEM is suggested probably by inhibiting the cadherin switch and angiogenesis.Copyright © 2019 Elsevier Inc. All rights reserved.

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