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Titolo:
Doxorubicin-peptide conjugates overcome multidrug resistance
Autore:
Mazel, M; Clair, P; Rousselle, C; Vidal, P; Scherrmann, JM; Mathieu, D; Temsamani, J;
Indirizzi:
Syntem, F-30000 Nimes, France Syntem Nimes France F-30000Syntem, F-30000 Nimes, France Hop Fernand Widal, INSERM, U26, F-75475 Paris 10, France Hop Fernand Widal Paris France 10 INSERM, U26, F-75475 Paris 10, France Inst Genet Mol, UMR5535, F-34293 Montpellier 5, France Inst Genet Mol Montpellier France 5 R5535, F-34293 Montpellier 5, France
Titolo Testata:
ANTI-CANCER DRUGS
fascicolo: 2, volume: 12, anno: 2001,
pagine: 107 - 116
SICI:
0959-4973(200102)12:2<107:DCOMR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLOOD-BRAIN-BARRIER; CELLS IN-VITRO; P-GLYCOPROTEIN; TUMOR-CELLS; CYCLOSPORINE-A; K562 CELLS; VINCRISTINE RESISTANCE; DRUG-DELIVERY; ADRIAMYCIN; CANCER;
Keywords:
blood-brain barrier; doxorubicin; multidrug resistance; peptide vector;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Temsamani, J Syntem, Parc Sci Georges Besse, F-30000 Nimes, France Syntem Parc Sci Georges Besse Nimes France F-30000 s, France
Citazione:
M. Mazel et al., "Doxorubicin-peptide conjugates overcome multidrug resistance", ANTI-CANC D, 12(2), 2001, pp. 107-116

Abstract

A well-known mechanism leading to the emergence of multidrug-resistant tumor cells is the overexpression of P-glycoprotein (P-gp), which is capable of lowering intracellular drug concentrations. To overcome this problem, we tested the capability of two peptide vectors that are able to cross cellular membranes to deliver doxorubicin in P-gp-expressing cells. The antitumor effect of peptide-conjugated doxorubicin was tested in human erythroleukemic (K562/ADR) resistant cells. The conjugate showed potent dose-dependent inhibition of cell growth against K562/ADR cells as compared with doxorubicinalone. Doxorubicin exhibited IC50 concentrations of 65 muM in the resistant cells, whereas vectorized doxorubicin was more effective with IC50 concentrations of 3 muM. After treatment of the resistant cells with verapamil, the intracellular levels of doxorubicin were markedly increased and consequent cytotoxicity was improved. In contrast, treatment of resistant cells with verapamil did not cause any further enhancement in the cell uptake nor inthe cytotoxic effect of the conjugated doxorubicin, indicating that the conjugate bypasses the P-gp. Finally, we show by the in situ brain perfusion method in P-gp-deficient and competent mice that vectorized doxorubicin bypasses the P-gp present at the luminal site of the blood-brain barrier. These results indicate that vectorization of doxorubicin with peptide vectors is effective in overcoming multidrug resistance. [(C) 2001 Lippincott Williams & Wilkins.].

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 12:18:27