Journal
CHEMBIOCHEM
Volume 17, Issue 18, Pages 1713-1718Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600368
Keywords
antitumour agents; bioinorganic chemistry; cancer; cobalt; cox inhibition
Funding
- Leverhulme Trust [ECF-2014-178]
- King's College London Faculty Graduate School International Studentship
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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.
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