A Breast Cancer Stem Active Cobalt(III)-Cyclam Complex Containing Flufenamic Acid with Immunogenic Potential.
Cancer Stem Cells
Cobalt
Damage-Associated Molecular Patterns
Immunotherapeutics
Non-Steroidal Anti-Inflammatory Drugs
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
05 Feb 2024
05 Feb 2024
Historique:
received:
23
11
2023
medline:
2
2
2024
pubmed:
8
12
2023
entrez:
8
12
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38063406
doi: 10.1002/anie.202317940
doi:
Substances chimiques
Cisplatin
Q20Q21Q62J
Flufenamic Acid
60GCX7Y6BH
cyclam
295-37-4
Coordination Complexes
0
Cobalt
3G0H8C9362
Antineoplastic Agents
0
Heterocyclic Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202317940Subventions
Organisme : NCI NIH HHS
ID : R01CA258421-01
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA258421-01
Pays : United States
Informations de copyright
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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