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Titolo:
beta(2)-microglobulin induces apoptosis in HL-60 human leukemia cell line and its multidrug resistant variants overexpressing MRP1 but lacking Bax oroverexpressing P-glycoprotein
Autore:
Wu, CH; Rastegar, M; Gordon, J; Safa, AR;
Indirizzi:
Indiana Univ, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA IndianaUniv Indianapolis IN USA 46202 oxicol, Indianapolis, IN 46202 USA Indiana Univ, Ctr Canc, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 r Canc, Indianapolis, IN 46202 USA
Titolo Testata:
ONCOGENE
fascicolo: 48, volume: 20, anno: 2001,
pagine: 7006 - 7020
SICI:
0950-9232(20011025)20:48<7006:BIAIHH>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLASS-I MOLECULES; PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; BREAST-CANCER; T-CELLS; GENE-EXPRESSION; POLY(ADP-RIBOSE) POLYMERASE; INDEPENDENT APOPTOSIS; PROSTATE-CANCER; MELANOMA-CELLS;
Keywords:
multidrug resistance; beta(2)-microglobulin; caspases; apoptosis; leukemia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
80
Recensione:
Indirizzi per estratti:
Indirizzo: Safa, AR Indiana Univ, Dept Pharmacol & Toxicol, 1044 W Walnut R4-119, Indianapolis, IN 46202 USA Indiana Univ 1044 W Walnut R4-119 Indianapolis IN USA 46202 2 USA
Citazione:
C.H. Wu et al., "beta(2)-microglobulin induces apoptosis in HL-60 human leukemia cell line and its multidrug resistant variants overexpressing MRP1 but lacking Bax oroverexpressing P-glycoprotein", ONCOGENE, 20(48), 2001, pp. 7006-7020

Abstract

In this study, we examined whether exogenous beta (2)-microglobulin (beta M-2) can induce apoptosis in the drug sensitive HL-60 leukemia cell line and its drug resistant variants and investigated the molecular mechanism of beta (2)m-induced apoptosis. Our data revealed that beta (2)m is very significantly down-regulated in two multidrug resistant variants of the HL-60 cells: (a) the MRP1-bearing, Bax-deficient HL-60/ADR cell line, and (b) the P-glycoprotein (P-gp) overexpressing HL-60/VCR cell line. However, exogenous beta (2)m induced similar levels of apoptosis in HL-60 cells and these drugresistant variants. beta (2)m-induced apoptosis in HL-60 and HL-60/VCR cells was associated with decreased mitochondrial membrane potential (Delta psim) but did not affect Delta psim in HL-60/ADR cells. Surprisingly, cyclosporin A (CsA), a known inhibitor of the mitochondrial permeability transition (MPT) pore, inhibited beta (2)m-induced apoptosis in HL-60/ADR cells but not in HL-60 and HL-60/VCR cells, suggesting that the pro-apoptotic effect of beta (2)m in these cells is not through MPT pore formation. Furthermore,beta (2)m induced the release of cytochrome c and the apoptosis-inducing factor (AIF) from mitochondria in HL-60 and HL-60/VCR cells, but not in HL-60/ADR cells. Additionally, z-VAD-fmk, a general inhibitor of caspases whichinhibited cytochrome c release in HL-60 and HL-60/VCR cells, had no effecton AIF release in any of these cell lines, but inhibited beta (2)m-inducedapoptosis in all three cell lines. However, Western blot analysis revealedthat caspases-1, -3, -6, -8, and -9 are not activated during beta (2)m-induced apoptosis in these cells. Therefore, beta (2)m-induces apoptosis through an unknown caspase-dependent mitochondrial pathway in HL-60 and HL-60/VCR cells and by a Bax-independent, non-mitochodrial, caspase-dependent pathway in HL-60/ADR cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 06:30:30