Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Cell Death Dis ; 5: e1371, 2014 Aug 14.
Article in English | MEDLINE | ID: mdl-25118931

ABSTRACT

Endostatin (ES) inhibits angiogenesis, reducing tumor growth in animal models. However, it has low therapeutic effect in human clinical trials. BAX is a member of the BCL-2 family of proteins; its proapoptotic (BH3) domain interacts with other members of the family in the cytoplasm, to induce apoptosis. Here, we fused the BAX BH3 domain with murine ES, to enhance ES potency. Endothelial cells specifically internalize the fusion protein ES-BAX. The presence of the BAX domain enhances endothelial cell death by apoptosis by 1.8-fold and diminishes microvessel outgrowth in the rat aortic ring assay by 6.5-fold. Daily injections of 15 µg of ES-BAX/g in tumor-bearing mice reduce tumor weight by 86.9% as compared with ES-treated animals. Co-immunoprecipitation assays confirmed that ES-BAX interacts with members of the BCL-2 family. Also, ES interacts with BCL-2, BCL-XL, and BAK in endothelial cell lysates, suggesting a potential new mechanism for the apoptosis induction by ES. The superiority of the ES-BAX antiangiogenic effect indicates that this fusion protein could be a promising therapeutic alternative to treat cancer.


Subject(s)
Angiogenesis Inhibitors/toxicity , Apoptosis/drug effects , Endostatins/toxicity , bcl-2-Associated X Protein/metabolism , Amino Acid Sequence , Angiogenesis Inhibitors/therapeutic use , Animals , Cell Line, Tumor , Endostatins/genetics , Endostatins/therapeutic use , Escherichia coli/metabolism , Kidney Neoplasms/drug therapy , Male , Mice , Mice, Inbred BALB C , Molecular Sequence Data , NIH 3T3 Cells , Protein Binding , Protein Structure, Tertiary , Rats , Rats, Sprague-Dawley , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/toxicity , Transplantation, Homologous , bcl-2-Associated X Protein/chemistry , bcl-2-Associated X Protein/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...