Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB
Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB
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DOI：
10.1002/ijc.23239
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发表时间：
2008-03-15
影响因子：
6.4
通讯作者：
Gartel, Andrei L.
中科院分区：
文献类型：
--
作者：
Bhat, Uppoor G.;Gartel, Andrei L.
最近，我们鉴定了一种名为ARC（4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-Pyrrolo [2，3-d] pyrimidine-5-carboxamide）的核苷类似物，其具有通用转录抑制剂的性质。在这里，我们报告了一组结直肠癌（CRC）细胞系ARC的特征。CRC细胞中ARC诱导的细胞死亡伴随着caspase-3裂解，并与抗凋亡蛋白Survivin和Mcl-1的下调以及Akt磷酸化的抑制相关。与此同时，结肠癌细胞系对众所周知的核苷类似物DRB（5，6-二氯-1-β-D-呋喃核糖基苯并咪唑）具有耐药性，该药物未能下调Mcl-1或生存素。总的来说，ARC可能是抗癌药物开发的一个有吸引力的候选者，靶向结肠癌细胞中的多种生存途径。(C)2007 Wiley-Liss，Inc.
Recently, we identified a nucleoside analog named ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-Pyrrolo[2,3-d]pyrimidine-5- carboxamide), which has the properties of a general transcriptional inhibitor. Here, we report the characterization of ARC on a panel of colorectal cancer (CRC) cell lines. Cell death induced by ARC in CRC cells was accompanied by caspase-3 cleavage and correlated with the downregulation of antiapoptotic proteins, survivin and Mcl-1 and with the inhibition of Akt phosphorylation. At the same time, colon cancer cell lines were resistant to the well-known nucleoside analog DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), which failed to downregulate Mcl-1 or survivin. Overall, ARC could represent an attractive candidate for anti-cancer drug development that targets multiple survival pathways in colon cancer cells. (C) 2007 Wiley-Liss, Inc.