Breast Cancer Stem Cell Potent Copper(II)–Non‐Steroidal Anti‐Inflammatory Drug Complexes |
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| Authors: | Janine N Boodram Iain J Mcgregor Peter M Bruno Paul B Cressey Dr Michael T Hemann Dr Kogularamanan Suntharalingam |
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| Institution: | 1. Department of Chemistry, King's College London, London, UK;2. The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA |
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| Abstract: | The breast cancer stem cell (CSC) potency of a series of copper(II)–phenanthroline complexes containing the nonsteroidal anti‐inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4 , selectivity kills breast CSC‐enriched HMLER‐shEcad cells over breast CSC‐depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC‐specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase‐2 (COX‐2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis. |
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| Keywords: | bioinorganic chemistry cancer COX inhibition nonsteroidal anti-inflammatory drugs reactive oxygen species |
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