Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.
Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.
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发表时间：
2011-12
影响因子：
2
通讯作者：
Eri Hikita;M. Arai;Sachiko Tanaka;K. Onda;H. Utsumi;Bo Yuan;H. Toyoda;T. Hirano
中科院分区：
文献类型：
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作者：
Eri Hikita;M. Arai;Sachiko Tanaka;K. Onda;H. Utsumi;Bo Yuan;H. Toyoda;T. Hirano
背景/目的探讨无机和有机砷化合物对人t淋巴母细胞白血病细胞的影响。材料与方法采用3-（4,5-二甲基噻唑-2-基）-2,5 -二苯基溴化四唑（MTT）法检测细胞增殖。采用Hoechst 33342染色法观察凋亡细胞形态。砷处理后细胞caspase-3/7活性测定。结果As(2)O(3)对MOLT-4和柔红霉素耐药MOLT-4/DNR细胞增殖的抑制浓度（50% IC(50)）分别为0.87和0.92 μM，对砷酸的抑制浓度分别为69.1和116.6 μM。这些砷化合物还能抑制丝裂原诱导的人外周血单个核细胞的增殖。6种有机砷化合物对白血病细胞增殖无抑制作用。As(2)O(3)和砷酸诱导白血病细胞凋亡，增加caspase-3/7活性。抗坏血酸和丁硫氨酸亚砜对白血病细胞增殖的抑制作用增强，n -乙酰- l-半胱氨酸抑制作用减弱。结论As(2)O(3)和砷酸通过谷胱甘肽耗竭和caspase-3/7激活抑制MOLT-4和多柔比星耐药MOLT-4/DNR细胞增殖并诱导细胞凋亡。有机砷化合物对白血病细胞增殖无抑制作用。无机砷化合物被认为是治疗t淋巴母细胞白血病的有效药物。
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.