Potentiation of Etoposide and Temozolomide Cytotoxicity by Curcumin and Turmeric Force in Brain Tumor Cell Lines

Abstract

We have investigated on the potentiation of etoposide (ETP) and temozolomide (TMZ) cytotoxicity in U-87MG glioblastoma and D283 medulloblastoma cell lines by curcumin (CUR) and turmeric force (TF), a nutraceutical formulation of turmeric, with the objective of assessing the potential for their adjuvant use in brain tumor chemotherapy. While U-87MG cell line was generally resistant to TMZ, IC50 values for CUR and TF were 37.33 and 30.75 µg/ml, respectively. TF is the only agent that demonstrated efficacy at the IC90 level. When CUR or TF was combined with ETP and TMZ, increased chemotherapeutic efficiency in the U-87MG cells was observed. TF is highly cytotoxic to D283 Med cell line compared to curcumin with an IC50 value of 1.55 ug/ml. Although both CUR and TF potentiated ETP and TMZ cytotoxicity, TF is more efficient than CUR in both U-87MG and D283 Med cell lines. Treatment of U-87MG cells with the triple combination of TMZ+ETP+TF induced a high percentage of apoptotic cells. Potential mechanisms that may explain evidence of synergy include down regulation of p10 and p53 mRNAs and increase in BAX/Bcl-2 mRNA ratio. These pre-clinical results suggest that TF may be useful as an adjuvant with ETP and TMZ for brain tumor chemotherapy.