A Breast Cancer Stem Cell-Selective, Mammospheres-Potent Osmium(VI) Nitrido Complex

被引：95
作者：
Suntharalingam, Kogularamanan [1 ]
Lin, Wei [1 ]
Johnstone, Timothy C. [1 ]
Bruno, Peter M. [2 ]
Zheng, Yao-Rong [1 ]
Hemann, Michael T. [2 ]
Lippard, Stephen J. [1 ,2 ]
机构：
[1] MIT, Dept Chem, Cambridge, MA 02139 USA
[2] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
来源：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 41期
关键词：
IDENTIFICATION; LIGANDS; DEATH;
D O I：
10.1021/ja508808v
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
The effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. The complex displays selective toxicity for HMLER breast cancer cells enriched with CD44-positive, CSC-like cells over the same cells having reduced CSC character. Remarkably, 1 also reduces the proportion of CSCs within a heterogeneous breast cancer cell population and irreversibly inhibits the formation of free-floating mammospheres to an extent similar to that of salinomycin, a natural product that targets CSCs. Detailed mechanistic studies reveal that in breast cancer cells 1 induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of 1 provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors.
引用
收藏
页码：14413 / 14416
页数：4
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