Characterization of antiproliferative potential and biological targets of a copper compound containing 4'-phenyl terpyridine

J Biol Inorg Chem. 2015 Sep;20(6):935-48. doi: 10.1007/s00775-015-1277-z. Epub 2015 Jun 16.

Abstract

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Caspase 3 / genetics
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper / chemistry
  • Copper / pharmacology*
  • DNA / chemistry
  • Epithelial Cells / drug effects
  • Fibroblasts / drug effects
  • Flow Cytometry
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Oxidative Stress
  • Proteomics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Pyridines / chemistry*
  • Serum Albumin / chemistry
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • Coordination Complexes
  • Proto-Oncogene Proteins c-bcl-2
  • Pyridines
  • Serum Albumin
  • bcl-2-Associated X Protein
  • Copper
  • DNA
  • CASP3 protein, human
  • Caspase 3