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    The mechanism of apoptosis in human acute promyelocytic leukemia cells treated with sorafenib and lithium chloride
    (2019) Ekinci, Aysun; Kaya, Safiye
    Objectives: This study was an investigation of the mechanisms of sorafenib (SOR) and lithium chloride (LiCl), whichcause apoptosis, in the acute promyelocytic leukemia (APL) HL-60 cell line.Methods: HL-60 cells were treated with 100 ?M of SOR, LiCl, and a combination of the 2 drugs, and a control group wasnot treated. Cells were collected after a period of 24, 48, and 72 hours, and cell proliferation and the apoptotic indexwere assessed with a hemocytometer and flow cytometry analysis. The level of caspase-3, phospho-glycogen synthasekinase-3 beta (p-GSK-3?), phospho-protein kinase B (p-AKT), phospho-extracellular-signal-regulated kinase (p-ERK),p38, phospho-c-Jun (p-c-Jun), and phospho-inhibitor kappa B (p-I?B?) were analyzed using the enzyme-linked immunosorbentassay method. The effects of the drugs on cell ultrastructure were evaluated with a transmission electronmicroscope (TEM).Results: Single and combination drug administration decreased cell proliferation and increased the apoptosis rate(p<0.01 for both). The increase in apoptosis in the SOR+LiCl group was greater than that of the SOR group (p<0.01);however, there was no significant increase compared with the LiCl group. While both drugs increased the caspase-3level (p<0.01 for both), LiCl increased caspase-3 activity more than SOR. Although p-GSK-3? levels decreased in theSOR group (p<0.01), levels increased in the LiCl group (p>0.05). Combined drug administration decreased the levelof p-AKT and p38 (p<0.01 for both); however, it did not significantly affect the level of p-ERK, p-I?B?, or p-c-Jun(p>0.05). TEM examination revealed severe lytic cytoplasmic damage and apoptotic morphology, an indication ofapoptosis.Conclusion: The results of this study demonstrated that in human APL cells treated with SOR and LiCl, increased apoptosisled to a decrease in tumor cells. This combination may become a preferred drug alternative for patients with APLand a mood disorder.