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

Author(s)
Suntharalingam, Kogularamanan; Lin, Wei; Johnstone, Timothy; Bruno, Peter Michael; Zheng, Yaorong; Hemann, Michael; Lippard, Stephen J.; ... Show more Show less
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Abstract
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.
Date issued
2014-09
URI
http://hdl.handle.net/1721.1/108805
Department
Massachusetts Institute of Technology. Department of Chemistry; Koch Institute for Integrative Cancer Research at MIT
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Suntharalingam, Kogularamanan et al. “A Breast Cancer Stem Cell-Selective, Mammospheres-Potent Osmium(VI) Nitrido Complex.” Journal of the American Chemical Society 136.41 (2014): 14413–14416. © 2014 American Chemical Society
Version: Final published version
ISSN
0002-7863
1520-5126

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