Abstract
A new approach for enzyme prodrug therapy for cancer was tested using human endothelial cells and two breast cancer cell lines in vitro. The concept is to use the human annexin V protein to selectively target the enzyme L-methioninase to the tumor vasculature. The major finding was that enzyme prodrug treatment using the L-methioninase-annexin V fusion protein and selenomethionine as the prodrug over 3 days was shown to be lethal to the endothelial cells and the cancer cells, while having little or no effect with the prodrug but with no fusion protein present. Thus, this new approach appears promising.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Annexin A5 / genetics
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Annexin A5 / metabolism
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Breast Neoplasms / blood supply
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology
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Carbon-Sulfur Lyases / genetics
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Carbon-Sulfur Lyases / metabolism
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Cell Line
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Cell Line, Tumor
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Electrophoresis, Polyacrylamide Gel
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Female
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Humans
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Kinetics
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Methanol / analogs & derivatives
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Methanol / metabolism
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Methanol / pharmacology
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Neovascularization, Pathologic / pathology
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Neovascularization, Pathologic / prevention & control
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Organoselenium Compounds / metabolism
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Organoselenium Compounds / pharmacology
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Prodrugs / metabolism
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Prodrugs / pharmacology*
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Protein Binding
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology*
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Selenomethionine / metabolism
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Selenomethionine / pharmacology*
Substances
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Annexin A5
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Organoselenium Compounds
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Prodrugs
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Recombinant Fusion Proteins
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methaneselenol
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Selenomethionine
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Carbon-Sulfur Lyases
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L-methionine gamma-lyase
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Methanol