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

Xiaoxia Guo, Bing Xu, Shuchita Pandey, Elisabeth Goessl, James Brown, Angel L. Armesilla, John L. Darling, Weiguang Wang

Research output: Contribution to journalArticle

Abstract

Most of the gemcitabine (dFdC) resistant cell lines manifested high NF?B activity. The NF?B activity can be induced by dFdC and 5-FU exposure. The chemosensitizing effect of disulfiram (DS), an anti-alcoholism drug and NF?B 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 NF?B 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.
Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalCancer Letters
Volume290
Issue number1
Early online date25 Sep 2009
DOIs
Publication statusPublished - 1 Apr 2010

Keywords

  • NFκB
  • breast cancer
  • colorectal cancer
  • disulfiram
  • gemcitabine resistance

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