Susceptibility to cytosine arabinoside (Ara-C)-induced cytotoxicity in human leukemia cell lines
Susceptibility to cytosine arabinoside (Ara-C)-induced cytotoxicity in human leukemia cell lines
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DOI：
10.1016/j.toxlet.2004.04.014
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发表时间：
2004-09-10
影响因子：
3.5
通讯作者：
Ishikawa, M
中科院分区：
文献类型：
--
作者：
Kanno, S;Higurashi, A;Ishikawa, M
阿糖胞苷(1-β-D-arabinofuranosylcytosine，Ara-C)是治疗急性白血病最重要的抗代谢化疗药物。我们检测了一些典型的人类白血病细胞系，NALM-6，MOLT-4，Jurkat，U937和HL-60对Ara-C诱导的细胞死亡的敏感性的差异。肿瘤抑制基因p53高表达的NALM-6细胞对Ara-C最敏感。Ara-C对P53缺失的人白血病细胞株U937和HL-60的作用较小。易感性和Ara-C摄取之间并不总是相关的。所有白血病细胞产生的活性氧(ROS)均增加。野生型P53的化学抑制剂吡氟菊酯-α可改善Ara-C对NALM-6和MOLT-4的细胞毒性，但不能改善Jurkat、U937或HL-60的细胞毒性。我们的数据表明，Ara-C诱导细胞死亡的机制是一种常见的机制，涉及ROS产生增加和P53依赖的细胞死亡。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Cytosine arabinoside (1-beta-D-arabinofuranosylcytosine; Ara-C) is the most important antimetabolite chemotherapeutic drug used for acute leukemia. We examined the difference in susceptibility to Ara-C-induced cell death among a number of typical human leukemia cell lines, NALM-6, MOLT-4, Jurkat, U937 and HL-60. NALM-6, which had a high expression level of p53, a tumor suppressor gene, was most susceptible to Ara-C. U937 and HL-60, with p53-null human leukemia cell lines were little affected by Ara-C. There was not always a correlation between susceptibility and the uptake of Ara-C. The production of reactive oxygen species (ROS) was increased in all leukemia cells. Pifithrin-alpha, a chemical inhibitor of wild-type p53, ameliorated the cytotoxicity of Ara-C in NALM-6 and MOLT-4, but not Jurkat, U937 or HL-60. Our data suggest that the mechanism of Ara-C-induced cell death is a common one, involving an increase in the production of ROS and p53-dependent cell death. (C) 2004 Elsevier Ireland Ltd. All rights reserved.