Diallyl disulfide, a chemopreventive agent in garlic, induces multidrug resistance-associated protein 2 expression.
Biochem Biophys Res Commun
; 324(2): 937-45, 2004 Nov 12.
Article
en En
| MEDLINE
| ID: mdl-15474518
ABSTRACT
The organosulfur compounds (OSCs), present in garlic, are studied for their protective effect against human cancers. P-glycoprotein (P-gp) and multidrug resistance protein 2 (Mrp2) are two transporters involved in the defense of cells and in the development of multidrug resistance. Whereas OSCs increase glutathione S-transferase activity (GST), Mrp2 plays a role in the transport of glutathione (GSH)-conjugates. In this study, we have investigated the effect of two OSCs, diallyl disulfide (DADS) and S-allyl cysteine (SAC), on P-gp and Mrp2 expression in renal brush-border membranes. By Western blot analysis, our results show that DADS induces Mrp2 expression (by 7-fold), which correlates with the rise of GST activity and GSH levels. Surprisingly, a co-administration of OSC with cisplatin, an anticancer drug, significantly increased Mrp2 gene and protein expression (by 30-fold), suggesting that DADS could potentiate the effects of cisplatin. Interestingly, SAC and cisplatin in co-treatment decreased P-gp protein expression and mdr1b isoform mRNA levels. In addition, modulation of the mdr1b isoform and Mrp2 by cisplatin was completely abolished by a glutathione precursor, N-acetyl cysteine. These results indicate that OSCs present in a garlic-rich diet might alter chemotherapeutic treatments using P-gp or Mrp2 substrates.
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Banco de datos:
MEDLINE
Asunto principal:
Proteínas Ribosómicas
/
Extractos Vegetales
/
Anticarcinógenos
/
Cisteína
/
Proteínas de Saccharomyces cerevisiae
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Proteínas Mitocondriales
/
Disulfuros
/
Compuestos Alílicos
/
Ajo
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2004
Tipo del documento:
Article