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

doi:10.1002/ange.201510443

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

Chemistry

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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 language	English
Pages (from-to)	2895-2900
Journal	ANGEWANDTE CHEMIE INTERNATIONAL EDITION IN ENGLISH
Volume	128
Issue number	8
Early online date	25 Jan 2016
DOIs	https://doi.org/10.1002/ange.201510443
Publication status	Published - 18 Feb 2018

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

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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AU - Boodram, Janine N.

AU - Mcgregor, Iain J.

AU - Bruno, Peter M.

AU - Cressey, Paul Brian

AU - Hemann, Michael T.

AU - Suntharalingam, Kogularamanan

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N2 - 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.

AB - 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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ER -

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

Abstract

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