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|Título:||Interaction between doxorubicin and the resistance modifier stilbene on multidrug resistant mouse lymphoma and human breast cancer cells|
|Autor:||Ferreira, Maria-Jose U.|
|Editora:||INT INST ANTICANCER RESEARCH|
|Citação:||ANTICANCER RESEARCH. - Vol. 26, n. 5A (SEP-OCT 2006), p. 3541-3546|
|Resumo:||The hydroxystilbene trans-3,5,3,4-tetrahydroxystilbene (piceatannol) (1), isolated from the methanol extract of Euphorbia lagascae defatted seeds, was methylated to yield the derivatives trans-3,5,3,4'-tetramethoxystilbene (2), (trans-3,5-dihydroxy-3', 4'-dimethoxystilbene) (3) and trans-3,5,3'-trihydroxy4'-methoxystilbene (4). The structures of the compounds were assigned by spectroscopic methods (IR, H-1-NMR, C-13-NMR and MS). The ability of piceatannol (1) and the three methylated derivatives to modulate the transport activity of P-glycoprotein (P-gp) and apoptosis induction on the L5178 mouse lymphoma cell line containing the human MDR1 gene was studied by flow cytometry. The reversal of multidrug-resistance (MDR) was investigated by measuring the accumulation of rhodamine-123, a fluorescent substrate analog of doxorubicin, in cancer cells. Verapamil was applied as a positive control. For the evaluation of the compounds as apoptosis inducers, tumor cells were stained with FITC-labelled annexin-V and propidium iodide. The tetramethylated derivative (2) was found to be a powerful inhibitor of P-gp activity. Compounds I and 2 showed an increased apoptotic effect in the MDR subline, the most active being piceatannol (1). Furthermore, in the combination chemotherapy model, the interaction between doxorubicin and the resistance modifier 2 was studied in vitro. The results of checkerboard experiments indicated that the type of interaction was additive between doxorubicin and compound 2 on the human MDR1 gene-transfected mouse lymphoma cells. However, in the MCF7/dox human breast cancer cells, the interaction was non-additive. The degree of additive and non-additive interactions were close to the borderline of the FIX values corresponding to the two types of interactions.|
|Aparece nas colecções:||FF - Produção Científica 2000-2009|
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