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

Ana Soraia Mendo, Sara Figueiredo, Catarina Roma-Rodrigues, Paula A. Videira, Zhen Ma, Mario Diniz, Miguel Larguinho, P.M. Costa, Joao C. Lima, Armando J. L. Pombeiro, Pedro V. Baptista, Alexandra R. Fernandes

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)935-948
Number of pages14
JournalJournal Of Biological Inorganic Chemistry
Volume20
Issue number6
DOIs
Publication statusPublished - Sep 2015

Keywords

  • Anticancer drug
  • Apoptosis
  • Biomedicine
  • DNA damage
  • Nucleic acid
  • BOVINE SERUM-ALBUMIN
  • HEAT-SHOCK PROTEINS
  • CELL-CYCLE
  • CANCER-CELLS
  • DNA CLEAVAGE
  • COMET ASSAY
  • ENDOPLASMIC-RETICULUM
  • ANTICANCER ACTIVITY
  • LIGANDS SYNTHESIS
  • PROSTATE-CANCER

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