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Titolo:
SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance
Autore:
Barancik, M; Bohacova, V; Kvackajova, J; Hudecova, S; Krizanova, O; Breier, A;
Indirizzi:
Slovak Acad Sci, Inst Mol Physiol & Genet, Bratislava 84334, Slovakia Slovak Acad Sci Bratislava Slovakia 84334 et, Bratislava 84334, Slovakia Slovak Acad Sci, Heart Res Inst, Bratislava 84233, Slovakia Slovak Acad Sci Bratislava Slovakia 84233 st, Bratislava 84233, Slovakia
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 1, volume: 14, anno: 2001,
pagine: 29 - 36
SICI:
0928-0987(200108)14:1<29:SASIOP>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; CANCER CELL-LINE; DIFFERENTIAL EXPRESSION; VINCRISTINE RESISTANCE; PHOSPHORYLATION SITES; LINKER REGION; L1210; ACCUMULATION; BIOCHEMISTRY; ACTIVATION;
Keywords:
mouse leukaemia cells L1210; multidrug resistance; P-glycoprotein; vincristine; p38-MAPK; protein kinase inhibitors; SB203580;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Breier, A Slovak Acad Sci, Inst Mol Physiol & Genet, Vlarska 5, Bratislava84334, Slovakia Slovak Acad Sci Vlarska 5 Bratislava Slovakia 84334 4, Slovakia
Citazione:
M. Barancik et al., "SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance", EUR J PH SC, 14(1), 2001, pp. 29-36

Abstract

P-glycoprotein (P-gp) is the plasma membrane transport pump responsible for efflux of chemotherapeutic agents from cells and is one of the systems that secures multidrug resistance (MDR) of neoplastic cells. In the present study, drug sensitive L1210 and multidrug resistant L1210/VCR (characterizedby overexpression of P-gp) mouse leukemic cell lines were used as an experimental model. We have found that SB203580. a specific inhibitor of p38-MAPK pathway. significantly reduced the degree of the vincristine resistance in L1210/VCR cells. This phenomenon was accompanied by a decrease in the LC50 value of vincristine from 3.203 +/- 0.521 to 0.557 +/- 0.082 muM. The LC50 value of sensitive cells for vincristine was about 0.011 muM. The effect of SB203580 on L1210/VCR cells was associated with significantly increased intracellular accumulation of [H-3]-vincristine in the concentration dependent manner. Prolonged exposure of resistant cells to 30 muM SB203580 did neither significantly influence the gene expression of P-gp, nor change the protein levels of p38-MAPK. Western blot analysis revealed that the MDR phenotype in L1210/VCR cells was associated with increased level and activity of cytosolic p38-MAPK. In resistant cells, the enhanced phosphorylation of both. p38-MAPK and ATF-2 (endogenous substrate for p38-MAPK) was found as well. In conclusion we could remark that SB203580, an inhibitor of p38 kinasepathway, reversed the MDR resistance of L1210/VCR cells. MDR phenotype of these cells is connected with increased levels and activities of p38-MAPK. These findings point to the possible involvement of the p38-MAPK pathway inthe modulation of P-gp mediated multidrug resistance in the L1210/VCR mouse leukemic cell line. However, the mechanisms of SB203580 action should be further investigated. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:17:10