Ellagic Acid Enhances the Antitumor Efficacy of Bevacizumab in an In Vitro Glioblastoma Model.
Animals
Antimetabolites, Antineoplastic
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
Apoptosis
/ drug effects
Bevacizumab
/ pharmacology
Brain Neoplasms
/ drug therapy
Bromodeoxyuridine
/ pharmacology
Cell Line, Tumor
DNA Repair
/ drug effects
Drug Resistance, Neoplasm
Drug Synergism
Ellagic Acid
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Glioblastoma
/ drug therapy
Rats
Cancer therapy
Ellagic acid
Glioblastoma
Temozolomide
Journal
World neurosurgery
ISSN: 1878-8769
Titre abrégé: World Neurosurg
Pays: United States
ID NLM: 101528275
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
25
06
2019
revised:
30
08
2019
accepted:
31
08
2019
pubmed:
14
9
2019
medline:
29
1
2020
entrez:
14
9
2019
Statut:
ppublish
Résumé
The 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. Rat 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), O EA 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. This 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.
Sections du résumé
BACKGROUND
BACKGROUND
The 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.
METHODS
METHODS
Rat 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), O
RESULTS
RESULTS
EA 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.
CONCLUSIONS
CONCLUSIONS
This 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.
Identifiants
pubmed: 31518741
pii: S1878-8750(19)32425-8
doi: 10.1016/j.wneu.2019.08.257
pii:
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Antineoplastic Agents, Immunological
0
Ellagic Acid
19YRN3ZS9P
Bevacizumab
2S9ZZM9Q9V
Bromodeoxyuridine
G34N38R2N1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e59-e65Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.