Targeting biliverdin reductase overcomes multidrug resistance in leukemia HL60 cells.

BACKGROUND/AIM Altered redox status has been reported to play a significant role in the development of multidrug resistance (MDR) in leukemia cells. Human biliverdin reductase (hBVR) has been recently identified as a major cytoprotectant; however, its role in MDR has not been yet investigated. In the present study we evaluated the possible role of hBVR in MDR development in the human HL60 leukemia cell line. MATERIALS AND METHODS The relationship between hBVR and MDR was examined using the drug-sensitive HL60 cells and the drug-resistant HL60 subline, HL60/ADR. A possible chemosensitization by siRNA pre-treatment was also investigated. RESULTS We observed that hBVR expression, protein, and enzymatic activity were significantly increased in multidrug-resistant HL60 leukemia cells. We also found that knockdown of hBVR reverses multidrug resistance in resistant leukemic HL60 cells by a ROS-dependent mechanism. CONCLUSION hBVR plays a pivotal role in the development of multidrug resistance in human HL60 leukemia cells.