Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Cell Biol Int ; 45(3): 518-527, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32068315

RESUMEN

Arginine-deprivation therapy is a rapidly developing metabolic anticancer approach. To overcome the resistance of some cancer cells to this monotherapy, rationally designed combination modalities are needed. In this report, we evaluated for the first time indospicine, an arginine analogue of Indigofera plant genus origin, as potential enhancer compound for the metabolic therapy that utilizes recombinant human arginase I. We demonstrate that indospicine at low micromolar concentrations is selectively toxic for human colorectal cancer cells only in the absence of arginine. In arginine-deprived cancer cells indospicine deregulates some prosurvival pathways (PI3K-Akt and MAPK) and activates mammalian target of rapamycin, exacerbates endoplasmic reticulum stress and triggers caspase-dependent apoptosis, which is reversed by the exposure to translation inhibitors. Simultaneously, indospicine is not degraded by recombinant human arginase I and does not inhibit this arginine-degrading enzyme at its effective dose. The obtained results emphasize the potential of arginine structural analogues as efficient components for combinatorial metabolic targeting of malignant cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Arginina/deficiencia , Neoplasias/patología , Norleucina/análogos & derivados , Arginasa/metabolismo , Arginina/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Norleucina/química , Norleucina/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Especificidad por Sustrato/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA