The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells

Paul Brian Cressey; Arvin Eskandari; Peter M. Bruno; Chunxin Lu; Michael T. Hemann; Kogularamanan Suntharalingam

doi:10.1002/cbic.201600368

The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells

Paul Brian Cressey, Arvin Eskandari, Peter M. Bruno, Chunxin Lu, Michael T. Hemann, Kogularamanan Suntharalingam

Chemistry

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Abstract

We report the cancer stem cell (CSC) potency of a novel cobalt(III)-cyclam complex, 1 bearing the nonsteroidal anti-inflammatory drug, naproxen. The cobalt(III)-cyclam complex, 1 displays selective potency for breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Additionally, 1 inhibits the formation of three-dimensional tumor-like mammospheres, and reduces their viability to a greater extent than clinically used breast cancer drugs; vinorelbine, cisplatin, and paclitaxel. The mammosphere-potency of 1 was enhanced in hypoxia-mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase-2 (COX-2) inhibition contribute to the cytotoxic mechanism of action of 1. To the best of our knowledge, 1 is the first cobalt-containing compound to show selective potency for CSCs over bulk cancer cells.

Original language	English
Pages (from-to)	1713-1718
Number of pages	6
Journal	CHEMBIOCHEM
Volume	17
Issue number	18
Early online date	5 Jul 2016
DOIs	https://doi.org/10.1002/cbic.201600368
Publication status	Published - 11 Aug 2016

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10.1002/cbic.201600368

The Potent Inhibitory Effect_Supplementary Information_CRESSEY_Accepted30June2016_GREEN AAMAccepted author manuscript, 1.25 MB
The Potent Inhibitory Effect_CRESSEY_Accepted30June2016_GREEN AAMfiguresAccepted author manuscript, 501 KB

Metal-based Drugs and Bioinspired Nanomaterials for Targeting Cancer Stem Cells.
Suntharalingam, R. (Primary Investigator) & Booth, P. (Co-Investigator)
Leverhulme Trust
1/10/2014 → 30/09/2017
Project: Research

Cite this

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title = "The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells",

abstract = "We report the cancer stem cell (CSC) potency of a novel cobalt(III)-cyclam complex, 1 bearing the nonsteroidal anti-inflammatory drug, naproxen. The cobalt(III)-cyclam complex, 1 displays selective potency for breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Additionally, 1 inhibits the formation of three-dimensional tumor-like mammospheres, and reduces their viability to a greater extent than clinically used breast cancer drugs; vinorelbine, cisplatin, and paclitaxel. The mammosphere-potency of 1 was enhanced in hypoxia-mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase-2 (COX-2) inhibition contribute to the cytotoxic mechanism of action of 1. To the best of our knowledge, 1 is the first cobalt-containing compound to show selective potency for CSCs over bulk cancer cells.",

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AU - Lu, Chunxin

AU - Hemann, Michael T.

AU - Suntharalingam, Kogularamanan

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AB - We report the cancer stem cell (CSC) potency of a novel cobalt(III)-cyclam complex, 1 bearing the nonsteroidal anti-inflammatory drug, naproxen. The cobalt(III)-cyclam complex, 1 displays selective potency for breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Additionally, 1 inhibits the formation of three-dimensional tumor-like mammospheres, and reduces their viability to a greater extent than clinically used breast cancer drugs; vinorelbine, cisplatin, and paclitaxel. The mammosphere-potency of 1 was enhanced in hypoxia-mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase-2 (COX-2) inhibition contribute to the cytotoxic mechanism of action of 1. To the best of our knowledge, 1 is the first cobalt-containing compound to show selective potency for CSCs over bulk cancer cells.

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The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells

Abstract

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Metal-based Drugs and Bioinspired Nanomaterials for Targeting Cancer Stem Cells.

Cite this