Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells
Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells
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DOI：
10.1002/ijc.20435
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发表时间：
2004-11-10
影响因子：
6.4
通讯作者：
Min, BH
中科院分区：
文献类型：
--
作者：
Noh, EJ;Kang, SW;Min, BH
由于精氨酸脱亚胺酶（ADI; EC 3.5.3.6）通过将细胞阻滞在G（1）期来抑制细胞增殖，我们测试了其对地塞米松（DEX）诱导的细胞死亡的协同作用，地塞米松也通过G（1）细胞周期阻滞来诱导细胞凋亡。ADI以剂量依赖性方式抑制人白血病CEM细胞增殖并诱导其凋亡。ADI和DEX同时处理对DNA断裂和LDH释放有协同作用。此外，ADI对DEX耐药的CEM细胞发挥其抗增殖活性。ADI抑制c-myc的表达，c-myc是细胞增殖和凋亡的潜在关键调节因子，并增加p27（Kip 1）细胞周期蛋白依赖性激酶抑制剂的表达。这些结果表明，ADI通过G（1）细胞周期阻滞（涉及c-myc下调和p27（Kip 1）上调）有效增加DEX对人白血病CEM细胞的抗癌作用。(C)2004 Wiley-Liss，Inc.
Since arginine deiminase (ADI; EC 3.5.3.6) inhibits cell proliferation by arresting cells in the G(1) phase, we tested its synergistic effect on cell death induced by dexamethasone (DEX), which also induces apoptosis by G(1) cell cycle arrest. ADI inhibited cell proliferation and induced apoptosis in human leukemic CEM cells in a dose-dependent manner. Simultaneous treatment with ADI and DEX showed synergistic effects on DNA fragmentation and LDH release. In addition, ADI exerted its anti-proliferative activity against DEX-resistant CEM cells. ADI suppressed expression of c-myc, a potential key regulator of cell proliferation and apoptosis, and increased expression of p27(Kip1) cyclin-dependent kinase inhibitor. These results suggest that ADI efficiently increases the anti-cancer effect of DEX on human leukemic CEM cells through G(1) cell cycle arrest involving downregulation of c-myc and upregulation of p27(Kip1). (C) 2004 Wiley-Liss, Inc.