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.
The breast cancer stem cell (CSC) potency of aseries 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,s electivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells.F urthermore, 4 reduces the formation, size,a nd viability of mammospheres, to ag reater extent than salinomycin, ap otassium ionophore knowntoselectively 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.T he former induces DNAd amage, activates JNK and p38 pathways, and leads to apoptosis.
The synthesis of colloidal semiconductor nanocrystals (NCs) from single-source precursors offers simplified manufacturing processes at the cost of reduced atom efficiency.
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