Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells.
Leuk Res
; 38(3): 377-82, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24461365
ABSTRACT
The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a diazeniumdiolate group necessary for the release of NO as well as an arylating ring. In this study, we research the mechanism by which JS-K kills a murine erythroleukemia cell line and determine the roles of NO and arylation in the process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP kinase pathways. This correlates with the activation of the tumor suppressor FoxO3a and increased expression of various caspases, leading to apoptosis. The arylating capability of JS-K appears to be sufficient for inducing these biological effects. Overall, these data suggest that JS-K kills tumor cells by arylating and inactivating signaling molecules that block the activation of a tumor suppressor.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Compostos Azo
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Pró-Fármacos
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Regulação Leucêmica da Expressão Gênica
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Doadores de Óxido Nítrico
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Citotoxinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article