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Modulating the Chemical and Biological Properties of Cancer Stem Cell-Potent Copper(II)-Nonsteroidal Anti-Inflammatory Drug Complexes

Department of Chemistry, King’s College London, London SE1 1DB, UK
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Academic Editor: Derek J. McPhee
Molecules 2019, 24(9), 1677; https://doi.org/10.3390/molecules24091677
Received: 5 April 2019 / Revised: 23 April 2019 / Accepted: 27 April 2019 / Published: 29 April 2019
(This article belongs to the Special Issue Metal Anticancer Complexes)
Copper(II) complexes bearing nonsteroidal anti-inflammatory drugs (NSAIDs) are known to potently kill cancer stem cells (CSCs), a subpopulation of tumour cells with high metastatic and relapse fidelity. One of the major disadvantages associated to these copper(II) complexes is their instability in the presence of strong cellular reductants (such as ascorbic acid). Here we present a biologically stable copper(II)-NSAID complex containing a bathocuproinedisulfonic acid disodium ligand and two indomethacin moieties, Cu(bathocuproinedisulfonic acid disodium)(indomethacin)2, 2. The copper(II) complex, 2 kills bulk breast cancer cells and breast CSC equally (in the sub-micromolar range) and displays very low toxicity against non-tumorigenic breast and kidney cells (IC50 value > 100 µM). Three-dimensional cell culture studies show that 2 can significantly reduce the number and size of breast CSC mammospheres formed (from single suspensions) to a similar level as salinomycin (an established anti-breast CSC agent). The copper(II) complex, 2 is taken up reasonably by breast CSCs and localises largely in the cytoplasm (>90%). Cytotoxicity studies in the presence of specific inhibitors suggest that 2 induces CSC death via a reactive oxygen species (ROS) and cyclooxygenase isoenzyme-2 (COX-2) dependent apoptosis pathway. View Full-Text
Keywords: metallodrugs; bioinorganic chemistry; copper; cancer stem cells metallodrugs; bioinorganic chemistry; copper; cancer stem cells
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MDPI and ACS Style

Shin, J.; Eskandari, A.; Suntharalingam, K. Modulating the Chemical and Biological Properties of Cancer Stem Cell-Potent Copper(II)-Nonsteroidal Anti-Inflammatory Drug Complexes. Molecules 2019, 24, 1677. https://doi.org/10.3390/molecules24091677

AMA Style

Shin J, Eskandari A, Suntharalingam K. Modulating the Chemical and Biological Properties of Cancer Stem Cell-Potent Copper(II)-Nonsteroidal Anti-Inflammatory Drug Complexes. Molecules. 2019; 24(9):1677. https://doi.org/10.3390/molecules24091677

Chicago/Turabian Style

Shin, Jimin, Arvin Eskandari, and Kogularamanan Suntharalingam. 2019. "Modulating the Chemical and Biological Properties of Cancer Stem Cell-Potent Copper(II)-Nonsteroidal Anti-Inflammatory Drug Complexes" Molecules 24, no. 9: 1677. https://doi.org/10.3390/molecules24091677

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