Membrane-associated cytotoxicity induced by realgar in promyelocytic leukemia HL-60 cells

Abstract

Realgar has been shown to have a therapeutic effect against acute promyelocytic leukemia (APL) by inducing apoptosis. However, there is little data about the effects of it on plasma membrane. In the present study, the cytotoxicity of realgar to HL-60 cells including its inhibiting cell growth, inducing apoptosis and bringing about membrane toxicity was investigated. It was suggested that realgar could significantly suppress the proliferation of HL-60 cells in a dose-dependent manner by 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium bromide (MTT) assay and the IC50 value was 5.67 microM. Flow cytometric analysis revealed that treatment with realgar resulted in increased percentages of apoptotic cells in a dose-dependent manner. On the other hand, membrane lipid peroxidation level, lactate dehydrogenase (LDH) leakage and membrane surface topography alterations were investigated to assess the membrane toxicity induced by realgar. Treatment with realgar at different concentrations accelerated membrane lipid peroxidation, potentiated LDH leakage, which was consistent with enhanced disorganization of membrane surface observed by atomic force microscopy (AFM). These results suggested that such membrane toxicity induced by realgar might play an important role in the process of apoptotic induction and could be considered as one of mechanisms underlying the cytotoxicity of realgar.