Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line.

ABSTRACT

Taking into account that multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment and as a continuation of our efforts to overcome this problem we report the evaluation of one cyclic selenoanhydride (1) and ten selenoesters (2-11) in MDR human colon adenocarcinoma Colo 320 cell line. The most potent derivatives (1, 9-11) inhibited the ABCB1 efflux pump much stronger than the reference compound verapamil. Particularly, the best one (9) was 4-fold more potent than verapamil at a 10-fold lower concentration. Furthermore, the evaluated derivatives exerted a potent and selective cytotoxic activity. In addition, they were strong apoptosis inducers as the four derivatives triggered apoptotic events in a 64-72% of the examined MDR Colo 320 human adenocarcinoma cells.