Mixed copper-platinum complex formation could explain synergistic antiproliferative effect exhibited by binary mixtures of cisplatin and copper-1,10-phenanthroline compounds: An ESI-MS study.

Cisplatin, cis-diammineplatinum(II) dichloride, is a metal complex used in clinical practice for the treatment of cancer. Despite its great efficacy, it causes adverse reactions and most patients develop a resistance to cisplatin. To overcome these issues, a multi-drug therapy was introduced as a modern approach to exploit the drug synergy. A synergistic effect had been previously found when testing binary combinations of cisplatin and three copper complexes in vitro, namely, Cu(phen)(OH2)2(OClO3)2, [Cu(phen)2(OH2)](ClO4)2 and [Cu(phen)2(H2dit)](ClO4)2,(phen=1,10-phenanthroline, H2dit=imidazolidine-2-thione), against the human acute T-lymphoblastic leukaemia cell line (CCRF-CEM). In this work [Cu(phen)2(OH2)](ClO4)2 was also tested in combination with cisplatin against cisplatin-resistant sublines of CCRF-CEM (CCRF-CEM-res) and ovarian (A2780-res) cancer cell lines. The tested combinations show a synergistic effect against both the types of resistant cells. The possibility that this effect was caused by the formation of new adducts was considered and mass spectra of solutions containing cisplatin and one of the three copper complexes at a time were measured using electrospray ionisation at atmospheric-pressure mass spectrometry (ESI-MS). A mixed complex was detected and its stoichiometry was assessed on the basis of the isotopic pattern and the results of tandem mass spectrometry experiments. The formed complex was found to be [Cu(phen)(OH)μ-(Cl)2Pt(NH3)(H2O)](+).
AuthorsTiziana Pivetta, Viola Lallai, Elisa Valletta, Federica Trudu, Francesco Isaia, Daniela Perra, Elisabetta Pinna, Alessandra Pani
JournalJournal of inorganic biochemistry (J Inorg Biochem) Vol. 151 Pg. 107-14 (Oct 2015) ISSN: 1873-3344 [Electronic] United States
PMID26021964 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Coordination Complexes
  • Organometallic Compounds
  • Phenanthrolines
  • copper-1,10-phenanthroline
  • Platinum
  • Copper
  • Cisplatin
  • Antineoplastic Agents (chemistry, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cisplatin (chemistry, pharmacology)
  • Coordination Complexes (chemistry, pharmacology)
  • Copper (chemistry, pharmacology)
  • Drug Synergism
  • Humans
  • Molecular Structure
  • Organometallic Compounds (chemistry)
  • Phenanthrolines (chemistry)
  • Platinum (chemistry)
  • Spectrometry, Mass, Electrospray Ionization

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