Abstract

BACKGROUND: Chronic myelogenous leukemia (CML) has unsatisfactory treatment efficacy at present. As the major component of red orpiment, tetra-arsenic tetra-sulfide (As4S4) has been recently used in treating leukemia, but with unclear mechanism targeting CML. MicroRNA (miR) is a group of endogenous non-coding RNAs regulating pathogenesis. MiR181 has been shown to exert important roles in tumor progression. The relationship between miR181 and As4S4 in inducing K562 cell apoptosis, however, is still unclear.

MATERIAL AND METHODS: CML cell line K562 was cultured in vitro in a control group and in groups receiving various dosages (20 μM and 40 μM) of As4S4. MTT assay was employed to detect the effect on K562 cell survival. MiR181 expression was quantified by real-time PCR. MTT assay and assay kit were used to determine K562 cell survival and caspase 3 expression. Cell apoptosis was assessed by flow cytometry. Bcl-2 expression was determined by real-time PCR and Western blotting.

RESULTS: As4S4 significantly suppressed proliferation of K562 cells (p<0.05) and decreased miR181 expression, and increased caspase3 activity compared to the control group. It can induce K562 cell apoptosis via remarkably down-regulating mRNA and protein expressions of Bcl-2 (p<0.05).

CONCLUSIONS: As4S4 can facilitate K562 cell apoptosis via down-regulating miR181, inhibiting Bcl02 expression, and enhancing apoptotic protein caspase3 activity.

Keywords: bcl-2-Associated X Protein, Caspase 14, Caspase Inhibitors, Genes, bcl-2, Tacrine