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

The effect of a newly developed osmium(VI) nitrido complex, <b>1</b>, 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, <b>1</b> 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 <b>1</b> induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of <b>1</b> provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors