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The Potent Inhibitory Effect of a Naproxen‐Appended Cobalt(III)‐Cyclam Complex on Cancer Stem Cells
Author(s) -
Cressey Paul B.,
Eskandari Arvin,
Bruno Peter M.,
Lu Chunxin,
Hemann Michael T.,
Suntharalingam Kogularamanan
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600368
Subject(s) - naproxen , potency , cyclam , chemistry , cancer stem cell , pharmacology , cancer research , cisplatin , drug , cobalt , cancer , biochemistry , in vitro , medicine , chemotherapy , pathology , alternative medicine , organic chemistry , metal , inorganic chemistry
We report the potency against cancer stem cells (CSCs) of a new cobalt(III)‐cyclam complex ( 1 ) that bears the nonsteroidal anti‐inflammatory drug, naproxen. The complex displays selective potency for breast CSC‐enriched HMLER‐shEcad cells over breast CSC‐depleted HMLER cells. Additionally, it inhibited the formation of three‐dimensional tumour‐like mammospheres, and reduced their viability to a greater extent than clinically used breast cancer drugs (vinorelbine, cisplatin and paclitaxel). The anti‐mammosphere potency of 1 was enhanced under hypoxia‐mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase‐2 (COX‐2) inhibition contribute to the cytotoxic mechanism 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.