Disulfiram/copper complex inhibiting NFkappaB activity and potentiating cytotoxic effect of gemcitabine on colon and breast cancer cell lines.
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.
Research Institute in Healthcare Science, University of Wolverhampton, UK.
Xiaoxia
X
Guo
Bing
B
Xu
Shuchita
S
Pandey
Elisabeth
E
Goessl
James
J
Brown
Angel L
AL
Armesilla
John L
JL
Darling
Weiguang
W
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D003300:Copper; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase; D004221:Disulfiram; D005472:Fluorouracil; D000093542:Gemcitabine