Thursday, August 22nd, 2019

 

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Title:
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.
Results:
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).
Conclusion:
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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