Disulfiram/copper complex inhibiting NFkappaB activity and potentiating cytotoxic effect of gemcitabine on colon and breast cancer cell lines

Cancer Lett. 2010 Apr 1;290(1):104-13. doi: 10.1016/j.canlet.2009.09.002. Epub 2009 Sep 25.

Abstract

Most of the gemcitabine (dFdC) resistant cell lines manifested high NFkappaB activity. The NFkappaB activity can be induced by dFdC and 5-FU exposure. The chemosensitizing effect of disulfiram (DS), an anti-alcoholism drug and NFkappaB inhibitor, and copper (Cu) on the chemoresistant cell lines was examined. The DS/Cu complex significantly enhanced the cytotoxicity of dFdC (resistant cells: 12.2-1085-fold) and completely reversed the dFdC resistance in the resitant cell lines. The dFdC-induced NFkappaB activity was markedly inhibited by DS/Cu complex. The data from this study indicated that DS may be used in clinic to improve the therapeutic effect of dFdC in breast and colon cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism*
  • Copper / pharmacology*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disulfiram / pharmacology*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Electrophoretic Mobility Shift Assay
  • Female
  • Fluorouracil / pharmacology
  • Gemcitabine
  • Humans
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism
  • Ribonucleoside Diphosphate Reductase
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • Copper
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Thymidylate Synthase
  • Disulfiram
  • Fluorouracil
  • Gemcitabine