pyrimidinones and vosaroxin

MEK inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination treatment of voreloxin with the MEK inhibitor TAK-733 on HL60 myeloid leukemia cells.. MAPK activity, cell viability, apoptosis, oxidative stress induction and AIF (apoptosis-inducing factor) distribution were assessed in HL60 cells cultured with each drug alone or with both drugs.. TAK-733 alone at 5 μM significantly reduced MAPK activity and did not influence viability and apoptosis in HL60 cells. Voreloxin at concentration of 0.03-0.48 μM reduced cell viability and increased apoptosis rate. Incubation with both drugs caused further inhibition of cell viability and increased apoptosis associated with generation of reactive oxygen species (ROS) and nuclear translocation of AIF.. Combination of TAK-733 and voreloxin can exert a synergistic anticancer effect in myeloid leukemia cells.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Inducing Factor; Cell Nucleus; Cell Survival; Drug Synergism; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; MAP Kinase Kinase Kinases; Microscopy, Confocal; Naphthyridines; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Reactive Oxygen Species; Thiazoles