Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis

Background: Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin. Materials and Methods: The activity of the hydantoin derivatives were investigated in another MDR cancer model, namely Colo 205/S sensitive and Colo 320/R resistant colon carcinoma cells respectively, having normal or overexpressed ABCB1 systems. Results: Among the hydantoin derivatives evaluated, BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the concentration of 4 mg/l on the Colo 320/R cells, compared to the positive control, verapamil. Conclusion: The derivatives did not induce apoptosis of Colo 320/R resistant colon carcinoma cells, indicating that these hydantoin compounds are potent efflux pump inhibitors (EPI) without affecting the signalling pathways that regulate apoptosis