Ras-targeting action of thiopurines in the presence of reactive nitrogen species.
Biochemistry
; 49(18): 3965-76, 2010 May 11.
Article
en En
| MEDLINE
| ID: mdl-20377193
ABSTRACT
Thiopurine drugs are commonly used in the treatment of certain cancers, autoimmune disorders, organ transplant rejection, and bowel disease. Because long-term treatment with thiopurines for certain diseases is common, the cytotoxic effects associated with chronic exposure to thiopurine drugs are inevitable. The results shown in this study indicate that the oncogenic Ras in model cancer cell lines forms a complex with thioguanine nucleotide that is derived from long-term treatment with thiopurines. This study also showed that the Ras thioguanine nucleotide binary complex is likely to be a direct target of a redox agent, resulting in downregulation of the oncogenic Ras. This study proposes a radical-based molecular mechanism for the path of Ras-targeting thiopurines used in conjunction with redox agents. Given that Ras plays a central role in cellular signaling pathways, any interference with Ras activity by thiopurines and redox agents has the potential for devastating cytotoxic effects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tioguanina
/
Proteínas ras
/
Especies de Nitrógeno Reactivo
/
Neoplasias
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Biochemistry
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos