A Breast Cancer Stem Active Cobalt(III)-Cyclam Complex Containing Flufenamic Acid with Immunogenic Potential

Jiaxin Fang, Owamagbe N. Orobator, Chibuzor Olelewe, Ginevra Passeri, Kuldip Singh, Samuel G. Awuah, Kogularamanan Suntharalingam

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article numbere202317940
JournalAngewandte Chemie - International Edition
Volume63
Issue number6
DOIs
StatePublished - Feb 5 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Keywords

  • Cancer Stem Cells
  • Cobalt
  • Damage-Associated Molecular Patterns
  • Immunotherapeutics
  • Non-Steroidal Anti-Inflammatory Drugs

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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