title: Tetra-arsenic tetra-sulfide induces cell cycle arrest and apoptosis in retinoic acid-resistant acute promyelocytic leukemia cells.
abstract: 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 As4S4in retinoic acid-resistant acute promyelocytic leukemia (APL) therapy remains unclear. In the present study, the signaling of the cytotoxic effects induced by As4S4on retinoic acid-resistant APL NB4-R1 cells was investigated. A time-dependent increase in cell death and DNA cleavage was observed following As4S4treatment. 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. As4S4induced 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.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: He
authors.affiliation: Institute of Xi'an Blood Bank, Shaanxi Blood Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
keywords: NB4-R1 cells; acute promyelocytic leukemia; apoptosis; cell cycle; tetra-arsenic tetra-sulfide