To observe the effect of combining ellagic acid (EA), a natural phenol present in fruits and vegetables, and temozolomide (TMZ) on the proliferation and expression profile of C6 glioma cell line.MATERIAL and METHODS: Rat C6 glioma cells were treated with 100-µM EA combined with 100 µM TMZ for 24, 48, and 72 hours (h). Cell proliferation and p53 and caspase-3 protein levels were evaluated using immunocytochemistry. Multi drug resistance 1 (MDR1), O6-methylguanine-DNA methyltransferase (MGMT), and apoptotic protein (caspase-3 and p53) expressions were assessed using reverse transcription polymerase chain reaction (RT-PCR).RESULTS: EA combined with TMZ conspicuously reduced the cell viability at all incubation times (p<0.001). EA significantly downregulated MGMT expression regardless of the presence of TMZ even at early hours (p<0.001). The combination therapy reduced MDR1 expression only on 48 h in comparison with TMZ alone. EA alone upregulated caspase-3 at 48 h but upregulated p53 at 48 and 72 h. The combined therapy enhanced the immunoreactivities of p53 and caspase-3 proteins independent of the treatment durations but not of the genes.CONCLUSION: EA combined with TMZ may have a potential antiproliferative efficacy by inhibiting MGMT expression and activating apoptotic protein, p53 and caspase-3, expression.
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.
Chitosan is a linear polysaccharide that has many biomedical applications. We compared the effects of chitosan, in both solution and membranous form, on intercellular adhesion of Swiss 3T3 mouse fibroblasts. Cells were grown as spheroidal cell cultures. Some control cell spheroids were cultured without chitosan and two experimental groups were cultured with chitosan. Chitosan in solution was used for one experimental group and chitosan in membranous form was used for the other. For each group, intercellular adhesion was investigated on days 5 and 10 of culture. Transmission electron microscopy revealed well-defined cellular projections that were more prominent in cells exposed to either membranous or solution forms of chitosan than to the chitosan-free control. Immunocytochemical staining of ICAM-1 and e-cadherin was used to determine the development of intercellular junctions. Compared to the weakly stained control, strong reactions were observed in both chitosan exposed groups at both 5 and 10 days. Cells were treated with 5-bromo-2-deoxyuridine (BrdU) and incubated with anti-BrdU primary antibody to assess proliferation. Both the solution and membranous forms of chitosan increased proliferation at both 5 and 10 days. Cellular viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The MTT assay indicated high cell viability; maximum viability was obtained with the solution form of chitosan at day 5. Chitosan exposure increased the number of intercellular junctions and showed a significant proliferative effect on 3T3 mouse fibroblasts.
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