Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation.
Pharmacology
; 92(1-2): 49-59, 2013.
Article
em En
| MEDLINE
| ID: mdl-23921841
ABSTRACT
BACKGROUND AND PURPOSE:
Geldanamycin and licochalcone A induce apoptosis in cancer cells. However, whether the combination of geldanamycin and licochalcone A-induced apoptosis in epithelial ovarian cancer cells is mediated by the formation of reactive oxygen species, leading to the activation of apoptotic caspase, has not been studied. EXPERIMENTALAPPROACH:
Using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3, we investigated the promoting effect of licochalcone A on geldanamycin-induced apoptosis.RESULTS:
Geldanamycin induced changes in apoptosis-related protein levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, cleavage of PARP-1, formation of reactive oxygen species and depletion of glutathione (GSH). Licochalcone A enhanced geldanamycin-induced apoptosis-related protein activation, formation of reactive oxygen species, caspase activation and cell death. The combined effect was inhibited by the addition of oxidant scavengers.CONCLUSIONS:
Licochalcone A may potentiate the apoptotic effect of geldanamycin on ovarian carcinoma cell lines by the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway. The apoptosis-promoting effect of licochalcone A may be mediated by its stimulatory action on the formation of reactive oxygen species and the depletion of GSH, which results in the activation of caspases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzoquinonas
/
Lactamas Macrocíclicas
/
Chalconas
/
Inibidores de Proteínas Quinases
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article