Abstract
Copper(ii) coordination complexes, 1 and 2, containing nonsteroidal anti-inflammatory drugs (NSAIDs) potently kill breast cancer stem cells (CSCs) and bulk breast cancer cells. Although detailed biological studies have been conducted to shed light on their mechanism of cytotoxicity, little is known about their molecular level mechanism of action. This biophysical study, aided by the preparation of a fluorophore-containing analogue, 3, reveals that the complexes operate by undergoing reduction to a copper(i) form and releasing the associated NSAIDs.
MeSH terms
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Biophysical Phenomena / drug effects*
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Breast Neoplasms / diagnostic imaging
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Breast Neoplasms / drug therapy
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Cell Survival / drug effects
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Coordination Complexes / chemistry*
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Coordination Complexes / pharmacology
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Copper / chemistry*
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Female
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Fluorescent Dyes / chemistry
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Humans
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Indomethacin / chemistry
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Naproxen / chemistry
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Neoplastic Stem Cells / drug effects*
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Optical Imaging / methods
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Oxidation-Reduction
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Reactive Oxygen Species / metabolism
Substances
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Antineoplastic Agents
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Coordination Complexes
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Fluorescent Dyes
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Reactive Oxygen Species
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Naproxen
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Copper
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Indomethacin