Wolverhampton Intellectual Repository and E-Theses >
Research Institutes >
Research Institute in Healthcare Science >
Cancer Research Group >
Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines.
this identifier to cite or link
to this item:
|Title: ||Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines.|
|Citation: ||International Journal of Cancer, 104 (4): 504-511|
|Publisher: ||Wiley InterScience|
|Journal: ||International Journal of Cancer.|
|Issue Date: ||2003 |
|PubMed ID: ||12584750|
|Additional Links: ||http://www3.interscience.wiley.com/journal/102526456/abstract?CRETRY=1&SRETRY=0|
|Abstract: ||5-Fluorouracil (5-FU) is the major chemotherapeutic component for colorectal cancer (CRC) and other types of solid tumours. Resistance of cancer cells to 5-FU is considered the major obstacle for successful chemotherapy. NF-kappaB is a transcription factor. Cancer cells with high NF-kappaB nuclear activity demonstrate robust chemo- and radio-resistance. We demonstrated that nuclear NF-kappaB activity in CRC cell lines, DLD-1 and RKO(WT), was significantly induced by 5-FU in a concentration- and time-dependent manner. 5-FU induced IkappaBalpha degradation and promoted both NF-kappaB nuclear translocation and its DNA binding activity. 5-FU treatment did not influence the activities of AP-1, AP-2, Oct-1, SP-1, CRE-B and TFIID. Disulfiram (DS), a clinically used anti-alcoholism drug, strongly inhibited constitutive and 5-FU-induced NF-kappaB activity in a dose-dependent manner. DS inhibited both NF-kappaB nuclear translocation and DNA binding activity but had no effect on 5-FU-induced IkappaBalpha degradation. Used in combination, DS significantly enhanced the apoptotic effect of 5-FU on DLD-1 and RKO(WT) cell lines and synergistically potentiated the cytotoxicity of 5-FU to both cell lines. DS also effectively abolished 5-FU chemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro. As DS has extensive preclinical and clinical experience, translating its anticancer usage from in vitro study to clinical trials is relatively straightforward.|
|MeSH: ||Active Transport, Cell Nucleus|
I-kappa B Proteins
Tumor Cells, Cultured
|Appears in Collections: ||Cancer Research Group|
|Files in This Item:|
There are no files associated with this item.
|Related articles on PubMed|
Inhibition of inducible NF-kappaB activity reduces chemoresistance to 5-fluorouracil in human stomach cancer cell line.
Uetsuka H, Haisa M, Kimura M, Gunduz M, Kaneda Y, Ohkawa T, Takaoka M, Murata T, Nobuhisa T, Yamatsuji T, Matsuoka J, Tanaka N, Naomoto Y
2003 Sep 10
|See all 142 articles|
All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.