title: Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.
abstract: OBJECTIVE
  To investigate the effects of inorganic and organic arsenic compounds on human T-lymphoblastoid leukemia cells.
  
  
  METHODS
  Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5¬diphenyltetrazolium bromide (MTT) assay. Apoptotic cell morphology was examined by cell staining with Hoechst 33342. Cellular caspase-3/7 activities were measured after arsenic treatment.
  
  
  RESULTS
  The inhibitory concentration by 50% (IC(50)) values of As(2)O(3) towards MOLT-4 and daunorubicin- resistant MOLT-4/DNR cell proliferation were 0.87 and 0.92 μM, while the values for arsenic acid were 69.1 and 116.6 μM, respectively. These arsenic compounds also inhibited mitogen-induced proliferation of human peripheral blood mononuclear cells. Six organic arsenic compounds did not inhibit leukemia cell proliferation. As(2)O(3) and arsenic acid induced apoptotic cell morphology and increased caspase-3/7 activity in the leukemia cells. Ascorbic acid and buthionine sulfoxide enhanced, while N-acetyl-L-cysteine abated, the suppressive effects of inorganic arsenic compounds on leukemia cell proliferation.
  
  
  CONCLUSIONS
  As(2)O(3) and arsenic acid inhibit proliferation and induce apoptosis in MOLT-4 and daunorubicine-resistant MOLT-4/DNR cells via glutathione-depletion and subsequent caspase-3/7 activation. Organic arsenic compounds have no inhibitory activity on the leukemia cell proliferation. Inorganic arsenic compounds are suggested as useful agents for treatment of T-lymphoblastoid leukemia.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hikita
authors.forename: Mariko
authors.initials: M
authors.lastname: Arai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.forename: Hiroya
authors.initials: H
authors.lastname: Utsumi
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis; D001151:Arsenic / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008956:Models, Chemical; D009930:Organic Chemicals / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D009930:Organic Chemicals; D013778:Tetrazolium Salts; D013844:Thiazoles; D019328:Buthionine Sulfoximine; D053148:Caspase 3; D053179:Caspase 7; C022616:thiazolyl blue; D001151:Arsenic; C017807:bisbenzimide ethoxide trihydrochloride; D001205:Ascorbic Acid; D000111:Acetylcysteine