Chou-Talalay Analysis: Exploring Synergistic Pharmacological Effects of 5-Fluorouracil and Curcumin for Dose Optimization

Background

5-Fluorouracil (5-FU) is a chemotherapy drug commonly used in the treatment of colon cancer. There is a significant drive to mitigate the limitations of 5-fluorouracil while maintaining its therapeutic potency by exploring the potential of using natural products such as curcumin in conjunction with 5-FU. Thus, the present study investigates the in vitro pharmacodynamic interaction between 5-FU and curcumin using the Chou-Talalay method in HT29 cell lines.

Materials and Methods

Initially, the estimation of half-maximal concentration of the medications against HCT116 and HT29 cell lines was performed by 3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide assay. Later, the combination effect was studied in HT29 cell lines by constant ratio experiment design.

Results and Discussion

The research findings revealed that the 5-FU and curcumin exhibit dose-dependent anti-proliferative activity in HCT116 and HT29 cells. Moreover, it was observed that HT29 cell lines are less sensitive to 5-FU than HCT116 cell lines, rather than curcumin was found to inhibit cell proliferation in both cell lines with no significant statistical difference (p <0.05). The Combination Index (CI) values of less than 1 for all the combined experimental ratios indicated the synergistic effect of the two compounds. The generated Dose Reduction Index (DRI) values for the combination imply for the favourable dose reduction in the treatment of colorectal cancer.

Conclusion

Significantly, the study indicates that 40:1 ratio of 5-FU to curcumin might represent an ideal proportion for co-administration using an appropriate delivery system.