Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform
Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform
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DOI：
10.1016/j.canlet.2011.11.009
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发表时间：
2012-04-01
期刊：
影响因子：
9.7
通讯作者：
Pillai, M. Radhakrishna
中科院分区：
文献类型：
--
作者：
Sobhan, Praveen K.;Seervi, Mahendra;Pillai, M. Radhakrishna
目前的癌症治疗方法是基于最初的肿瘤消退筛选来确定的，这些筛选主要杀死分化的肿瘤细胞，保留罕见的癌症干细胞（CSC）。由于罕见且难以表征，因此鉴定对它们有活性的化合物仍然是一个挑战。在表达线粒体的多个癌细胞系组中鉴定出侧群（SP）细胞！利用高通量成像评价细胞色素C-EGFP用于鉴定可能的候选药物。我们确定热休克蛋白90抑制剂作为潜在的代理商，SP细胞敏感的抗癌药物。Hsp 90抑制剂诱导Akt下调，导致蛋白酶体降解生存素和随后的线粒体凋亡。开发了用于鉴定靶向耐药侧群细胞的化合物的成功筛选平台。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Current cancer therapeutics are identified based on initial tumor regression screens that mostly kill differentiated tumor cells, sparing the rare cancer stem cells (CSCs). Being rare and difficult to characterize, it remains a challenge to identify compounds active against them. Side population (SP) cells identified in multiple cancer cell line panels expressing mitochondria! Cytochrome C-EGFP were evaluated for identifying possible drug candidates utilizing high-throughput imaging. We identified heat shock protein 90 inhibitors as potential agents to sensitize SP cells to anticancer drugs. Hsp90 inhibitors induced down regulation of Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis. A successful screening platform for identifying compounds targeting drug resistant side population cells was developed. (C) 2011 Elsevier Ireland Ltd. All rights reserved.