Ellagic Acid Enhances Antitumor Efficacy of Temozolomide in an in vitro Glioblastoma Model

Abstract

AIM: 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), 06-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.