Thursday, December 8th, 2022


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Combining Ellagic Acid with Bevacizumab Mediates the Cadherin Switch and Angiogenesis in a Glioblastoma Model
Authors:  Abdurrahman Çetin, M.D., and Burcu Biltekin, Ph.D.
  Objective: To observe the combining effect of ellagic acid (EA) with bevacizumab (BEV) on cadherin switch and angiogenesis of C6-glioma cell line.
Study Design:
Rat C6 glioma cells were treated with EA at 100 μM 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 (Br-dU) immunocytochemistry. Expression profiles for E-cadherin, N-cadherin, and vascular endothelial growth factor (VEGF) proteins were determined by real-time quantitative PCR (qPCR) and their protein levels by immunocytochemistry, subsequent to EA treatment combined with or without BEV.
EA in combination with BEV conspicuously reduced the cell viability of C6-glioma cells for all incubation times. EA upregulated the expression of E-cadherin both at gene and protein levels in a time-independent manner (p<0.001), regardless of the presence of BEV. Conversely, EA with and without BEV reduced N-cadherin expression and immunoreactivity at 48 and 72 hours (p<0.001). EA combined with BEV treatment downregulated the expression of angiogenic protein of VEGF (p<0.001), as well as reduced its immunoreactivity only at 72 hours (p<0.01).
The present study suggests a successful therapeutic efficacy of EA in combination with BEV, probably through inhibition of the cadherin switch and VEGF expression. EA may be an alternative treatment of drug-resistant gliomas, in combination with BEV.
Keywords:  bevacizumab; cadherins; ellagic acid; glioblastoma; glioma; VEGF; vascular endothelial growth factor
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