Concentration- Dependent Effects of Curcumin on 5-Fluorouracil Efficacy in Bladder Cancer Cells

Abstract

<br /> <strong><span style="font-size: small;">Purpose: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Curcumin (Cur), a herbal ingredient with anticancer properties, has been shown to inhibit growth of malignant cells in vivo and in vitro. However, studies on combination therapy of Cur with chemotherapeutic drugs have been limited. Here, effects of Cur on the cytotoxicity of 5-Fluorouracil (FU) were investigated with epithelial bladder cancer cells (EJ138) in vitro. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">EJ138 cells were treated with 5 and 15 μM of Cur and/ or 100 μM of FU. Cell viability was measured by sulforhodamine B colorimetric assay. The glucose concentration as an index of cell metabolism was evaluated by an enzymatic method. Total oxidant and antioxidant capacities were estimated by the ferrous oxidation-xylenol (FOX1) method and ferric reducing antioxidant power assay (FRAP), respectively. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Combination of 5 μM Cur with FU significantly reduced its cytotoxicity in EJ138 cells, while 15 μM Cur caused an opposite increase. Significant increase in glucose concentration at 24 h and decrease in the FRAP value at 48 h incubation was observed in cells treated with FU in combination with Cur. There were no significant changes in total </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">oxidant capacity with the combination therapy. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our findings suggest a crucial role of Cur concentration </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">in regulating chemotherapeutic agent-induced cytotoxicity. Further investigations are needed to understand the precise mechanisms of action of Cur and determine appropriate doses with combination therapy for clinical application against human cancers. </span></span>