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Titolo:
The novel synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437) causes apoptosis in acute promyelocytic leukemia cells through rapid activation of caspases
Autore:
Mologni, L; Ponzanelli, I; Bresciani, F; Sardiello, G; Bergamaschi, D; Gianni, M; Reichert, U; Rambaldi, A; Terao, M; Garattini, E;
Indirizzi:
Marioolegri Inst Pharmacol Res, Ctr Catullo & Daniela Borgomainerio, Mol Bi Mario Negri Inst Pharmacol Res Milan Italy I-20157 Borgomainerio, Mol Bi Osped Riuniti Bergamo, Div Ematol, I-24100 Bergamo, Italy Osped Riuniti Bergamo Bergamo Italy I-24100 atol, I-24100 Bergamo, Italy GALDERMA Res & Dev, Sophia Antipolis, Italy GALDERMA Res & Dev Sophia Antipolis Italy Dev, Sophia Antipolis, Italy
Titolo Testata:
BLOOD
fascicolo: 3, volume: 93, anno: 1999,
pagine: 1045 - 1061
SICI:
0006-4971(19990201)93:3<1045:TNSR6>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
LEUKOCYTE ALKALINE-PHOSPHATASE; COLONY-STIMULATING FACTOR; BREAST-CARCINOMA CELLS; CYTOCHROME-C; IN-VITRO; DIFFERENTIATION THERAPY; MELANOMA-CELLS; RAR-ALPHA; NB4 CELLS; LAMIN-A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Garattini, E Marioolegri Inst Pharmacol Res, Ctr Catullo & Daniela Borgomainerio, Mol Bi Mario Negri Inst Pharmacol Res Via Eritrea 62 Milan Italy I-20157
Citazione:
L. Mologni et al., "The novel synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437) causes apoptosis in acute promyelocytic leukemia cells through rapid activation of caspases", BLOOD, 93(3), 1999, pp. 1045-1061

Abstract

The synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), which was originally developed as an retinoic acid receptor (RAR)-gamma agonist, induces rapid apoptosis in all-trans retinoic acid (ATRA)sensitive and ATRA-resistant clones of the NB4 cell line, a widely used experimental model of acute promyelocytic leukemia (APL). In addition,the compound is apoptogenic in primary cultures of freshly isolated APL blasts obtained from a newly diagnosed case and an ATRA-resistant relapsed patient. NB4 cells in the S-phase of the cycle are most sensitive to CD437-triggered apoptosis. CD437-dependent apoptosis does not require de novo protein synthesis and activation of RAR-gamma or any of the other nuclear retinoic acid receptors. The process is preceded by rapid activation of a caspase-like enzymatic activity capable of cleaving the fluorogenic DEVD but not the fluorogenic YVAD tetrapeptide. Increased caspase activity correlates with caspase-3 and caspase-7 activation. Inhibition of caspases by z-VAD suppresses the nuclear DNA degradation observed in NB4 cells treated with CD437.as well as the degradation of procaspase-3 and pro-caspase-7. CD437-dependent activation of caspases is preceded by release Of cytochrome c from the mitochondria into the cytosol of treated cells. Leakage of cytochrome c lays upstream of caspase activation, because the phenomenon is left unaffectedby pretreatment of NB4 cells with z-VAD. Treatment of APL cells with CD437is associated with a caspase-dependent degradation of promyelocytic leukemia-RAR-alpha, which can be completely inhibited by z-VAD. (C) 1999 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 01:02:48