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SINGH, Karampal, SINGH, Kuldip, JOHNSON, Alice and SUNTHARALINGAM, Kogularamanan (2024). Anti‐Breast Cancer Stem Cell Properties of Silver(I)‐Non‐Steroidal Anti‐Inflammatory Drug Complexes. European Journal of Inorganic Chemistry.
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Abstract
The synthesis and characterisation of a series of silver(I) complexes (1–7) containing non‐steroidal anti‐inflammatory drugs (NSAIDs) and triphenylphosphine ligands is reported. The diclofenac‐containing silver(I) complex 1 exhibits micromolar potency towards bulk breast cancer cells and breast cancer stem cells (CSCs) cultured in monolayers. Notably, the silver(I) complex 1 displays up to 9.4‐fold higher potency towards three‐dimensional mammospheres than cisplatin (a clinically used anticancer metallodrug) and salinomycin (a breast‐CSC active small molecule). Mechanistic studies show that the silver(I) complex 1 readily interacts with thiol‐containing biomolecules in solution and elevates intracellular reactive oxygen species levels in breast CSCs. Interestingly the silver(I) complex 1 does not perturb cyclooxygenase‐2 (COX‐2) expression in breast CSCs and its cytotoxicity is unaffected in the presence of prostaglandin E2, implicative of a COX‐2 independent mechanism of action.
| Item Type: | Article |
|---|---|
| Additional Information: | ** Article version: VoR ** From Wiley via Jisc Publications Router ** Licence for VoR version of this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: issn 1434-1948; issn 1099-0682 **Article IDs: publisher-id: ejic202400133 **History: published_online 12-07-2024; rev-recd 22-05-2024; submitted 08-03-2024 |
| Uncontrolled Keywords: | reactive oxygen species, non-steroidal anti-inflammatory drugs, cancer stem cells, silver, antitumour agents |
| Identification Number: | https://doi.org/10.1002/ejic.202400133 |
| SWORD Depositor: | Colin Knott |
| Depositing User: | Colin Knott |
| Date Deposited: | 15 Jul 2024 10:47 |
| Last Modified: | 15 Jul 2024 10:47 |
| URI: | https://shura.shu.ac.uk/id/eprint/33948 |
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