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Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.

AbstractBACKGROUND/AIM:
To investigate the effects of inorganic and organic arsenic compounds on human T-lymphoblastoid leukemia cells.
MATERIALS AND 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.
CONCLUSION:
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.
AuthorsEri Hikita, Mariko Arai, Sachiko Tanaka, Kenji Onda, Hiroya Utsumi, Bo Yuan, Hiroo Toyoda, Toshihiko Hirano
JournalAnticancer research (Anticancer Res) Vol. 31 Issue 12 Pg. 4169-78 (Dec 2011) ISSN: 1791-7530 [Electronic] Greece
PMID22199276 (Publication Type: Journal Article)
Chemical References
  • Benzimidazoles
  • Organic Chemicals
  • Tetrazolium Salts
  • Thiazoles
  • HOE 33342
  • thiazolyl blue
  • Buthionine Sulfoximine
  • Caspase 3
  • Caspase 7
  • Arsenic
  • Ascorbic Acid
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Apoptosis
  • Arsenic (pharmacology)
  • Ascorbic Acid (pharmacology)
  • Benzimidazoles (pharmacology)
  • Buthionine Sulfoximine (pharmacology)
  • Caspase 3 (metabolism)
  • Caspase 7 (metabolism)
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Leukemia, T-Cell (drug therapy)
  • Leukocytes, Mononuclear (cytology)
  • Models, Chemical
  • Organic Chemicals (pharmacology)
  • T-Lymphocytes (drug effects)
  • Tetrazolium Salts (pharmacology)
  • Thiazoles (pharmacology)

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