title: Association of oxidative stress with realgar-induced differentiation in human leukemia HL-60 cells.
abstract: BACKGROUND
  Realgar (arsenic sulfide, As(4)S(4)) has been shown to have clinical efficacy in patients with newly diagnosed and relapsed acute promyelocytic leukemia. Mechanistic studies have demonstrated that realgar is able to induce cell differentiation.
  
  
  METHODS
  The oxidative stress in the realgar-induced differentiation was examined with human leukemia HL-60 cells. Cell differentiation was evaluated by the expression of cell surface antigen CD11b and nitroblue tetrazolium assay. The activities of catalase and superoxide dismutase were measured spectrophotometrically. Flow cytometry was used to assess cell cycle distribution and apoptosis, the cellular level of reactive oxygen species (ROS) and glutathione, as well as mitochondrial transmembrane potential (MTP).
  
  
  RESULTS
  The realgar-induced differentiation was enhanced by hydrogen peroxide, and preceded with drastic changes in ROS and catalase, as well as small changes in superoxide dismutase and the reduced form of glutathione. MTP values at 24 h were in linear proportion to the CD11b expression at 48 h when no apoptosis was observed.
  
  
  CONCLUSIONS
  Oxidative stress and stress-related MTP decrease are associated with realgar-induced differentiation in HL-60 cells.
authors.affiliation: Department of Chemical Biology, Capital Medical University School of Pharmaceutical Sciences, Beijing, PR China.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Shi
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Bao-Di
authors.initials: BD
authors.lastname: Gou
authors.forename: Tian-Lan
authors.initials: TL
authors.lastname: Zhang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000494:pharmacology*; D039481:CD11b Antigen / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D039481:CD11b Antigen; D017382:Reactive Oxygen Species; D013440:Sulfides; C058317:arsenic disulfide; D005978:Glutathione