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

Abstract

BACKGROUND/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.

• Authors: Eri Hikita, Mariko Arai, Sachiko Tanaka, Kenji Onda, Hiroya Utsumi, Bo Yuan, Hiroo Toyoda, Toshihiko Hirano
• Journal: Anticancer research (Anticancer Res) Vol. 31 Issue 12 Pg. 4169-78 (Dec 2011) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22199276 (Publication Type: Journal Article)

Chemical References

• Benzimidazoles
• Organic Chemicals
• Tetrazolium Salts
• Thiazoles
• Buthionine Sulfoximine
• Caspase 3
• Caspase 7
• thiazolyl blue
• Arsenic
• bisbenzimide ethoxide trihydrochloride
• 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)