Phenothiazines and selenocompounds: A potential novel combination therapy of multidrug resistant cancer

Abstract

Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. Results: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. Conclusion: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles,