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Titolo:
Resistance mechanisms associated with altered intracellular distribution of anticancer agents
Autore:
Larsen, AK; Escargueil, AE; Skladanowski, A;
Indirizzi:
Inst Gustave Roussy, Lab Biol & Pharmacol DNA Topoisomerases, CNRS UMR 8532, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805, F-94805 Villejuif, France Gdansk Tech Univ, Dept Pharmaceut Technol & Biochem, PL-80952 Gdansk, Poland Gdansk Tech Univ Gdansk Poland PL-80952 Biochem, PL-80952 Gdansk, Poland
Titolo Testata:
PHARMACOLOGY & THERAPEUTICS
fascicolo: 3, volume: 85, anno: 2000,
pagine: 217 - 229
SICI:
0163-7258(200003)85:3<217:RMAWAI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN TUMOR-CELLS; MDR-1 PROTEIN OVEREXPRESSION; CONJUGATE EXPORT PUMP; VACUOLAR H+-ATPASE; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; PLASMA-MEMBRANE; HL-60 CELLS; MRP GENE; CANCER CELL;
Keywords:
anticancer agents; P-glycoprotein; multidrug resistance protein; lung resistance protein; vesicular transport and turnover; intracellular pH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
128
Recensione:
Indirizzi per estratti:
Indirizzo: Larsen, AK Inst Gustave Roussy, Lab Biol & Pharmacol DNA Topoisomerases, CNRS UMR 8532, PR2, F-94805 Villejuif, France Inst Gustave Roussy PR2 Villejuif France F-94805 ejuif, France
Citazione:
A.K. Larsen et al., "Resistance mechanisms associated with altered intracellular distribution of anticancer agents", PHARM THERA, 85(3), 2000, pp. 217-229

Abstract

The resistance of tumor cells to anticancer agents remains a major cause of treatment failure in cancer patients. The term multidrug resistance (MDR)is used to define a resistance phenotype where cells are resistant to multiple drugs with no obvious structural resemblance and with different molecular targets. It is now clear that MDR is always multifactorial. The intracellular drug distribution is modified in many MDR cell lines, leading to increased drug sequestration in acidic vesicles, such as the trans-Golgi apparatus, recycling endosomes. and lysosomes, followed by transport to the plasma membrane and extrusion into the external medium. Since most anticancer agents target DNA or nuclear enzymes, sequestration of drug in cytoplasmic oganelles will lead to decreased drug-target interaction and thereby, decreased cytotoxicity. Altered intracellular drug distribution is usually associated with the expression of drug efflux pumps, such as the P-glycoprotein and the multidrug resistance protein. Another common modification in MDR cells is alkalization of the intracellular pH, The relationship between these different resistance mechanisms is reviewed and a model proposed that suggests why these different resistance mechanisms are co-expressed in multiple cell lines, (C) 2000 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 03:10:40