title: A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex.
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.
authors.affiliation: Department of Chemistry and ‡The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Kogularamanan
authors.initials: K
authors.lastname: Suntharalingam
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bruno
authors.forename: Yao-Rong
authors.initials: YR
authors.lastname: Zheng
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D017672:Nitrogen Compounds / Q000737:chemistry*; D009992:Osmium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017672:Nitrogen Compounds; D009992:Osmium