Buthionine sulfoximine enhancement of arsenic trioxide-induced apoptosis in leukemia and lymphoma cells is mediated via activation of c-Jun NH2-terminal kinase and up-regulation of death receptors
Buthionine sulfoximine enhancement of arsenic trioxide-induced apoptosis in leukemia and lymphoma cells is mediated via activation of c-Jun NH2-terminal kinase and up-regulation of death receptors
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DOI：
10.1158/0008-5472.can-06-0409
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发表时间：
2006-12-01
期刊：
影响因子：
11.2
通讯作者：
Jing, Yongkui
中科院分区：
文献类型：
--
作者：
Chen, Duo;Chan, Rosemarie;Jing, Yongkui
在 NB4、U937、Namalwa 和 Jurkat 细胞中研究了单独使用 As2O3 或与丁硫氨酸亚砜亚胺 (BSO) 联合处理诱导细胞凋亡的机制。 As2O3浓度<2μmol/L时可诱导NB4细胞和Namalwa细胞凋亡，但不诱导U937和Jurkat细胞凋亡。 As2O3 诱导的 NB4 细胞和 Namalwa 细胞凋亡与 H2O2 增加和 caspase 激活相关，但不激活 c-Jun NH2 末端激酶 (JNK)。 BSO (10 μ mol/L) 耗尽细胞内还原型谷胱甘肽而不诱导细胞凋亡，但与 1 μ mol/L As2O3 协同作用可诱导所有四种细胞系的细胞凋亡。这种协同作用与 JNK 激活相关。 As2O3 加 BSO 治疗（但单独使用 As2O3 则不然）增加了死亡受体 (DR) 5 蛋白和 caspase-8 裂解的水平。 JNK 抑制剂 SP600125 抑制 DR5 蛋白的增加，并减弱 As2O3 加 BSO 处理诱导的细胞凋亡。这些观察结果表明，JNK 激活的 DR 介导途径参与 As2O3 加 BSO 治疗诱导的细胞凋亡。
The mechanism of apoptosis induced by treatment with As2O3 alone or in combination with buthionine sulfoximine (BSO) was studied in NB4, U937, Namalwa, and Jurkat cells. As2O3 at concentrations < 2 mu mol/L induced apoptosis in NB4 cells and Namalwa cells but not in U937 and Jurkat cells. As2O3-induced apoptosis in NB4 cells and Namalwa cells correlated with increase of H2O2 and caspase activation without activation of c-Jun NH2-terminal kinase (JNK). BSO (10 mu mol/L) depleted the reduced form of intracellular glutathione without inducing apoptosis but synergized with 1 mu mol/L As2O3 to induce apoptosis in all four cell lines. This synergy correlated with JNK activation. Treatment with As2O3 plus BSO, but not with As2O3 alone, increased the levels of death receptor (DR) 5 protein and caspase-8 cleavage. The JNK inhibitor SP600125 inhibited the increase in DR5 protein and attenuated apoptosis induced by treatment with As2O3 plus BSO. These observations suggest that a DR-mediated pathway activated by JNK is involved in apoptosis induced by treatment with As2O3 plus BSO.