Antitumor activity of irinotecan with ellagic acid in C6 glioma cells

Abstract

OBJECTIVE:Irinotecan-based combination chemotherapies in malignant gliomas need to be examined. The aim of this study was to investigate the synergetic effect of ellagic acid, a natural polyphenolic antioxidant compound, with irinotecan, an inhibitor of topoisomerase I enzyme, on the growth, cadherin switch, and angiogenic processes of a glioma cell line. METHODS: A combination of 100 μM ellagic acid and 100 μM irinotecan was applied to rat C6 glioma cells for 24th, 48th, and 72nd h. The cell proliferation was evaluated by 5-bromo-2ʹ-deoxyuridine immunocytochemistry. The expression levels of vascular endothelial growth factor, E-cadherin, and N-cadherin were measured using real-time polymerase chain reaction and their immunoreactivities using immunocytochemistry. RESULTS: The treatment of irinotecan with combining ellagic acid enhanced antitumor activity and the synergistic effect of these reduced the cell proliferation of C6 glioma by inhibiting the cadherin switch and promoting the antiangiogenic processes. CONCLUSIONS: Further research is required to prove a negative relationship between C6 glial cell proliferation and irinotecan with ellagic acid application. Our preliminary data suggest that even with the extremely short-term application, irinotecan with ellagic acid may affect glioma cells at the level of gene and protein expression.

Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential

“…Treatment with high concentrations of punicalagin or ellagic acid significantly reduced cell viability and increased apoptosis in U87MG glioma cells [ 46 ], human peripheral blood mononuclear cells, and HeLa cells and significantly decreased the viability, migration, and invasiveness of MCF-7 and MDA-MB-231 breast cancer cells [ 47 ]. It was also found that the treatment inhibited the permeability, proliferation, migration, and formation of VEGF-induced tubules in human umbilical vein endothelial cells [ 48 ] to reduce the proliferation of C6 glioma cells, promoting antiangiogenic processes [ 49 ] and inhibit the proliferation of Caco2 human colon adenocarcinoma cells [ 50 ]. The above authors applied higher concentrations of these polyphenols than in the present study, in which no cell cycle changes were produced.…”

Kanserlere Yeni Hedefli Terapötik Yaklaşımlar

“…EA exhibits anti-tumour pharmacological properties, such as inhibition of tumour formation and growth via cell cycle arrest, induction of apoptosis (Edderkaoui et al 2008), and suppression of angiogenesis (Narayanan et al 1999). EA was also shown to have successful in vitro therapeutic efficacy when combined with chemotherapeutics in glioma cell lines via inhibiting cadherin switch, angiogenesis, inhibition of O6-methylguanine DNA methyltransferase expression, time-dependent inhibition of P-glycoprotein (MDR1), activating apoptotic protein, p53 and caspase-3, expression Cetin and Biltekin, 2020;Cetin et al 2022). Clinical research is needed to prove the short-term and long-term efficacy and safety of ellagic acid in brain tumors.…”