Use of the disulfiram/copper complex for breast cancer chemoprevention in MMTV-erbB2 transgenic mice

Mol Med Rep. 2015 Jul;12(1):746-52. doi: 10.3892/mmr.2015.3426. Epub 2015 Mar 4.

Abstract

The disulfiram/copper complex (DS/Cu) has been demonstrated to exert potent anti-tumor effects in various types of cancer. At present, whether DS/Cu has chemopreventive effects on breast cancer development remains to be fully elucidated. In the present study, using MMTV-erbB2 transgenic mice, it was identified for the first time that DS/Cu treatment was able to inhibit cell growth in breast cancer cells while sparing normal cells in vitro, in addition to delaying the development of mammary tumor development in MMTV-erbB2 transgenic mice in vivo. Morphological examination demonstrated that DS/Cu treatment resulted in cell proliferation inhibition and apoptosis activation in vitro and in vivo. Furthermore, the present study observed that DS/Cu may inhibit proliferation via inhibition of AKT and cyclin D1 signaling and promote apoptosis via c-Jun N-terminal kinase activation and suppression of nuclear factor κB signaling. These results suggested that DS/Cu treatment may be a promising therapy for the prevention of erbB2-positive breast cancer.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Chemoprevention
  • Copper / administration & dosage*
  • Cyclin D1
  • Disulfiram / administration & dosage*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Transgenic
  • Oncogene Protein v-akt / biosynthesis
  • Oncogene Protein v-akt / genetics
  • Receptor, ErbB-2 / genetics*
  • Signal Transduction / drug effects

Substances

  • Ccnd1 protein, mouse
  • Cyclin D1
  • Copper
  • Erbb2 protein, mouse
  • Receptor, ErbB-2
  • Oncogene Protein v-akt
  • Disulfiram