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

doi:10.1016/j.canlet.2009.09.002

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 journal › Article › peer-review

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 language	English
Pages (from-to)	104-113
Number of pages	10
Journal	Cancer Letters
Volume	290
Issue number	1
Early online date	25 Sept 2009
DOIs	https://doi.org/10.1016/j.canlet.2009.09.002
Publication status	Published - 1 Apr 2010

Keywords

NFκB
breast cancer
colorectal cancer
disulfiram
gemcitabine resistance

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10.1016/j.canlet.2009.09.002

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@article{dd42109bad7b4aac85a4fc9993c09b4a,

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

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.",

keywords = "NFκB, breast cancer, colorectal cancer, disulfiram, gemcitabine resistance",

author = "Xiaoxia Guo and Bing Xu and Shuchita Pandey and Elisabeth Goessl and James Brown and Armesilla, {Angel L.} and Darling, {John L.} and Weiguang Wang",

year = "2010",

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doi = "10.1016/j.canlet.2009.09.002",

language = "English",

volume = "290",

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journal = "Cancer Letters",

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TY - JOUR

T1 - Disulfiram/copper complex inhibiting NFκB activity and potentiating cytotoxic effect of gemcitabine on colon and breast cancer cell lines

AU - Guo, Xiaoxia

AU - Xu, Bing

AU - Pandey, Shuchita

AU - Goessl, Elisabeth

AU - Brown, James

AU - Armesilla, Angel L.

AU - Darling, John L.

AU - Wang, Weiguang

PY - 2010/4/1

Y1 - 2010/4/1

N2 - 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.

AB - 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.

KW - NFκB

KW - breast cancer

KW - colorectal cancer

KW - disulfiram

KW - gemcitabine resistance

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U2 - 10.1016/j.canlet.2009.09.002

DO - 10.1016/j.canlet.2009.09.002

M3 - Article

SN - 0304-3835

VL - 290

SP - 104

EP - 113

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

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

Abstract

Keywords

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