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Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes

Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes

Janine N Boodram, Iain J Mcgregor, Peter M Bruno, Paul B Cressey, Michael T Hemann, Kogularamanan Suntharalingam

Angew Chem Int Ed Engl. 2016 Feb 18;55(8):2845-50.

PMID: 26806362

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP69271983	Potassium ionophore II		69271-98-3	Price

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