Improving the therapeutic potential of endostatin by fusing it the BAX BH3 death domain
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Cell Death and Disease
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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 lg 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.
Como referenciar
CHURA-CHAMBI, R.M.; BELLINI, M.H.; JACYSYN, J.F.; ANDRADE, L.N.; MEDINA, L.P.; PRIETO da SILVA, A.R.B.; AMARANTE-MENDES, G.P.; MONGANTI, L. Improving the therapeutic potential of endostatin by fusing it the BAX BH3 death domain. Cell Death and Disease, v. 5, p. p. 1-10, 2014. DOI: 10.1038/cddis.2014.309. Disponível em: http://repositorio.ipen.br/handle/123456789/9025. Acesso em: 20 Mar 2026.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.