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

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

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)2895-2900
JournalANGEWANDTE CHEMIE INTERNATIONAL EDITION IN ENGLISH
Volume128
Issue number8
Early online date25 Jan 2016
DOIs
Publication statusPublished - 18 Feb 2018

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