title: Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent myelodysplastic syndrome-progressed leukemia cell line F-36p with complex karyotype including monosomy 7.
abstract: OBJECTIVE
  Acute myeloid leukemia progressed from myelodysplastic syndrome (MDS/AML) is generally incurable with poor prognosis for complex karyotype including monosomy 7 (-7). Qinghuang Powder (, QHP), which includes Qing Dai (Indigo naturalis) and Xiong Huang (realgar) in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains > 90% arsenic disulfide (As2S2). F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells.
  
  
  METHODS
  Cell proliferation was measured by an 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide (PI) exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a (GpA).
  
  
  RESULTS
  After treatment with As2S2 at concentrations of 0.5 to 16 μmol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations (IC50) of As2S2 against the proliferation of F-36p cells was 6 μmol/L. The apoptotic cells significantly increased in a dose-dependent mannar (P<0.05). The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner (P<0.05). Significant increases of CD235a-positive cells were concurrently observed (P<0.05) also in a dose-dependent manner.
  
  
  CONCLUSIONS
  As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7. The data suggest that QHP and/or As2S2 could be a potential candidate in the treatment of MDS or MDS/AML even with unfavorable cytogenetics.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan.
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Hu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
authors.forename: Rou
authors.initials: R
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D013440:Sulfides / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D016207:Cytokines; D013440:Sulfides; C058317:arsenic disulfide