A Breast Cancer Stem Cell-Selective, Mammospheres-Potent Osmium(VI) Nitrido Complex
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Lippard_A breast cancer.pdf
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Author(s)
Suntharalingam, Kogularamanan
Lin, Wei
Johnstone, Timothy
Bruno, Peter Michael
Zheng, Yaorong
Hemann, Michael
Lippard, Stephen J.
Date Issued
September 2014
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/ja508808v
