Tetra-arsenic tetra-sulfide induces cell cycle arrest and apoptosis in retinoic acid-resistant acute promyelocytic leukemia cells.

Previous studies have shown that the therapeutic action of tetra-arsenic tetra-sulfide (As4S4) is effective for acute promyelocytic leukemia. However, the molecular mechanism of the action of As4S4 in retinoic acid-resistant acute promyelocytic leukemia (APL) therapy remains unclear. In the present study, the signaling of the cytotoxic effects induced by As4S4 on retinoic acid-resistant APL NB4-R1 cells was investigated. A time-dependent increase in cell death and DNA cleavage was observed following As4S4 treatment. Changes in B-cell lymphoma 2 and Bax accompanied by the activation of caspase-3 and cleavage of poly ADP-ribose polymerase were observed as actions of As4S4. As4S4 induced an accumulation of NB4-R1 cells in the S and G2/M phases, as detected by flow cytometry. Therefore, the present results suggest that As4S4-mediated apoptosis in NB4-R1 cells involves a mitochondria-dependent pathway.