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

Abstract

Purpose: 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. Methods: 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. Results: 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 oxidant capacity with the combination therapy. Conclusion: Our findings suggest a crucial role of Cur concentration 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.

Keywords: Curcumin; 5-fluorouracil; bladder cancer.

Figure 1

Effect of Cur (5 and 15 µM), FU (100 µM) and Cur+FU on viability of EJ138 cells after 24, 48 and 72 h incubation by sulforhodamine B colorimetric assay. Values are means ± SD from at least three independent experiments. *p < 0.05 versus control (untreated cells), #p < 0.05 versus cells treated with FU alone and **p < 0.05 versus cells treated with Cur alone.

Figure 2

Effect of Cur (5 and 15 µM), FU (100 µM) and Cur+FU on medium glucose concentration (GLU) as an index of EJ138 cells metabolism after 24, 48 and 72 h incubation by enzymatic colorimetric assay. Values are means ± SD from at least three independent experiments. *p < 0.05 versus control (untreated cells)

Figure 3

Effect of Cur (5 and 15 µM), FU (100 µM) and Cur+FU on total antioxidant capacity of EJ138 cell medium after 24, 48 and 72 h incubation by colorimetric assay (FRAP). Values are means ± SD from at least three independent experiments. *p < 0.05 versus control (untreated cells)

Figure 4

Effect of Cur (5 and 15 µM), FU (100 µM) and Cur+FU on total oxidant capacity of EJ138 cell medium after 24, 48 and 72 h incubation by colorimetric assay (FOX1). Values are means ± SD from at least three independent experiments. *p < 0.05 versus control (untreated cells)