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

• Main Authors: Suntharalingam, Kogularamanan (Contributor), Lin, Wei (Contributor), Johnstone, Timothy (Contributor), Bruno, Peter Michael (Contributor), Zheng, Yaorong (Contributor), Hemann, Michael (Contributor), Lippard, Stephen J. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2017-05-11T14:18:32Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Grant CA034992)
Misrock Foundation (Fellowship)