Novel copper complexes as potential proteasome inhibitors for cancer treatment (Review)

Mol Med Rep. 2017 Jan;15(1):3-11. doi: 10.3892/mmr.2016.6022. Epub 2016 Dec 9.

Abstract

The use of metal complexes in the pharmaceutical industry has recently increased and as a result, novel metal‑based complexes have initiated an interest as potential anticancer agents. Copper (Cu), which is an essential trace element in all living organisms, is important in maintaining the function of numerous proteins and enzymes. It has recently been demonstrated that Cu complexes may be used as tumor‑specific proteasome inhibitors and apoptosis inducers, by targeting the ubiquitin‑proteasome pathway (UPP). Cu complexes have demonstrated promising results in preclinical studies. The UPP is important in controlling the expression, activity and location of various proteins. Therefore, selective proteasome inhibition and apoptotic induction in cancer cells have been regarded as potential anticancer strategies. The present short review discusses recent progress in the development of Cu complexes, including clioquinol, dithiocarbamates and Schiff bases, as proteasome inhibitors for cancer treatment. A discussion of recent research regarding the understanding of metal inhibitors based on Cu and ligand platforms is presented.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Coordination Complexes / therapeutic use*
  • Copper / chemistry
  • Copper / pharmacology
  • Copper / therapeutic use*
  • Drug Discovery*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / chemistry
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • Ubiquitin / metabolism

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Proteasome Inhibitors
  • Ubiquitin
  • Copper
  • Proteasome Endopeptidase Complex