Format:
Online-Ressource
ISSN:
1521-3773
Content:
Abstract: The cytotoxic and immunogenic‐activating properties of a cobalt (III)‐cyclam complex bearing the non‐steroidal anti‐inflammatory drug, flufenamic acid is reported within the context of anti‐cancer stem cell (CSC) drug discovery. The cobalt (III)‐cyclam complex 1 displays sub‐micromolar potency towards breast CSCs grown in monolayers, 24‐fold and 31‐fold greater than salinomycin (an established anti‐breast CSC agent) and cisplatin (an anticancer metallopharmaceutical), respectively. Strikingly, the cobalt (III)‐cyclam complex 1 is 69‐fold and 50‐fold more potent than salinomycin and cisplatin towards three‐dimensionally cultured breast CSC mammospheres. Mechanistic studies reveal that 1 induces DNA damage, inhibits cyclooxygenase‐2 expression, and prompts caspase‐dependent apoptosis. Breast CSCs treated with 1 exhibit damage‐associated molecular patterns characteristic of immunogenic cell death and are phagocytosed by macrophages. As far as we are aware, 1 is the first cobalt complex of any oxidation state or geometry to display both cytotoxic and immunogenic‐activating effects on breast CSCs.
In:
day:29
In:
month:12
In:
year:2023
In:
extent:10
In:
Angewandte Chemie / International edition, Weinheim : Wiley-VCH, 1962-, (29.12.2023) (gesamt 10), 1521-3773
Language:
English
DOI:
10.1002/anie.202317940
URN:
urn:nbn:de:101:1-2023123014080969476735
URL:
https://doi.org/10.1002/anie.202317940
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023123014080969476735
URL:
https://d-nb.info/1314845039/34
URL:
https://doi.org/10.1002/anie.202317940