Repurposing Drugs in Veterinary Cancer Treatment: Sodium Dichloroacetate and Omeprazole Exhibit Synergistic Cytotoxic Effects on Canine Oral Melanoma Cell Line
Introduction
Sodium Dichloroacetate (DCA) is a drug which provides a shift of the Warburg effect by stimulation of oxidative phosphorylation, reduction of tumoral growth and induction of apoptosis in different cancer types. Omeprazole (OMP) is a proton pump inhibitor which in cancer has been related to the regulation of extracellular and intracellular pH, potentially reduction of chemo-resistance, the improvement of other drug’s efficacy and induction of cell death. The aim of this study is to report a cytotoxic and synergistic effect that DCA and OMP presented on a canine oral melanoma cell line.
Methods
CBMT a canine oral melanoma cell line previously established at our laboratory was treated with different concentrations of DCA and OMP alone or in combination for 72 hours. The control group was treated with DMSO or Medium only. Cytotoxic effects were analyzed through the violet crystal method and read with the 570 mn spectrophotometer. Drug combination test for synergy was calculated using the Chou method and CalcSyn software to generate Combination Index (CI), CI values less than 1 are considered synergistic effects. ANOVA one-way and post testing Dunnet’s p<0.05 was considered statistically significant.
Results
The combination treatment of DCA and OMP showed higher cytotoxicity in a dose-dependent way. Every combination of DCA and OMP presented CI <1, therefore, DCA and OMP are synergistic cytotoxic drugs in CBMT cell line.
Conclusion
The combination treatment of DCA and OMP on CBMT cells exhibited cytotoxicity and synergistic effects and may be promising drugs on the treatment of canine oral melanoma.
Funding Information
This project is funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).