Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.
Djeha, A Hakim Hulme, Alison N Dexter, T Michael Mountain, Andrew Young, Lawrence S Searle, Peter F Kerr, David J Wrighton, Christopher J
Djeha, A Hakim
Hulme, Alison N
Dexter, T Michael
Mountain, Andrew
Young, Lawrence S
Searle, Peter F
Kerr, David J
Wrighton, Christopher J
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Abstract
Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.
Description
Date
2000-05
Publisher
Collections
Keywords
Head and Neck Cancer
Liver Cancer
Cancer Transplantation
Experimental Cancer
Cultured Tumour Cells
Liver Cancer
Cancer Transplantation
Experimental Cancer
Cultured Tumour Cells
Type
Article
Citation
Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954. 2000, 7 (5):721-31 Cancer Gene Ther.