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Title: A Cancer Stem Cell Potent Cobalt(III)-Cyclam Complex Bearing Two Tolfenamic Acid Moieties
Authors: Cressey, Paul B.
Eskandari, Arvin
Suntharalingam, Kogularamanan
First Published: 9-Feb-2017
Publisher: MDPI
Citation: Inorganics, 2017, 5 (1), 12
Abstract: Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs are a subtype of cancer cells with the ability to differentiate, self-renew, and form secondary or tertiary tumors. Current cancer treatments—including chemotherapy, radiation, and surgery—effectively remove bulk cancer cells but are unable to eliminate CSCs. Here, we present the synthesis, characterization, and anti-CSC properties of a cobalt(III)–cyclam complex bearing two tolfenamic acid moieties, 3. Notably, 3 displays sub-micromolar potency towards breast CSCs and bulk breast cancer cells. Detailed mechanistic studies show that 3 is taken up readily by breast CSCs, enters the nucleus, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 3 inhibits cyclooxygenase-2 (COX-2) expression in CSCs. The mechanism of action of 3 is similar to that of a naproxen-appended cobalt(III)–cyclam complex, 1 recently reported by our group. The advantage of 3 over 1 is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose.
DOI Link: 10.3390/inorganics5010012
ISSN: 2304-6740
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The following are available online at, Figures S1–S13.
Appears in Collections:Published Articles, Dept. of Chemistry

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