title: The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells.
abstract: 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.
authors.affiliation: Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Cressey
authors.affiliation: Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
authors.forename: Arvin
authors.initials: A
authors.lastname: Eskandari
authors.affiliation: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Building 76, 500 Main Street, Cambridge, MA, 02139, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bruno
authors.affiliation: Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
authors.forename: Chunxin
authors.initials: C
authors.lastname: Lu
authors.affiliation: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Building 76, 500 Main Street, Cambridge, MA, 02139, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.affiliation: Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK. kogularamanan.suntharalingam@kcl.ac.uk.
authors.forename: Kogularamanan
authors.initials: K
authors.lastname: Suntharalingam
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D009288:Naproxen / Q000737:chemistry / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D009942:Organometallic Compounds; D003035:Cobalt; D009288:Naproxen; D051546:Cyclooxygenase 2
keywords: antitumour agents; bioinorganic chemistry; cancer; cobalt; cox inhibition