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Titolo:
Augmentation of death ligand-induced apoptosis by aminopeptidase inhibitors in human solid tumor cell lines
Autore:
Sekine, K; Fujii, H; Abe, F; Nishikawa, K;
Indirizzi:
Nippon Kayaku Co Ltd, Pharmaceut Grp, Evaluat Grp, Drug Res Dept,R&D Div,Kita Ku, Tokyo 1158588, Japan Nippon Kayaku Co Ltd Tokyo Japan 1158588 v,Kita Ku, Tokyo 1158588, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 4, volume: 94, anno: 2001,
pagine: 485 - 491
SICI:
0020-7136(20011115)94:4<485:AODLAB>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED KILLER-CELLS; CYTOCHROME-C; SODIUM-BUTYRATE; LUNG-CANCER; FAS LIGAND; U937 CELLS; N CD13; UBENIMEX; BESTATIN; INDUCTION;
Keywords:
apoptosis; aminopeptidase; bestatin; death ligand; Fas;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Sekine, K Nippon Kayaku Co Ltd, Pharmaceut Grp, Evaluat Grp, Drug Res Dept,R&D Div,Kita Ku, 31-12 Shimo 3 Chome, Tokyo 1158588, Japan Nippon Kayaku Co Ltd 31-12 Shimo 3 Chome Tokyo Japan 1158588 an
Citazione:
K. Sekine et al., "Augmentation of death ligand-induced apoptosis by aminopeptidase inhibitors in human solid tumor cell lines", INT J CANC, 94(4), 2001, pp. 485-491

Abstract

We previously reported that the aminopeptidase inhibitor bestatin induced apoptosis in several human leukemia cell lines. The present study was performed to examine whether bestatin can also induce apoptosis in solid tumor cell lines. Bestatin alone exhibited neither direct growth inhibition nor induction of apoptosis in the tumor cell lines examined. However, it significantly augmented the growth-inhibitory effect and induction of apoptosis by agonistic. anti-Fas antibody (CH11). The augmentation by bestatin was also observed with other death ligands including tumor necrosis factor-alpha (TNF-alpha) in EBC-1 cells, a cell line sensitive to these death ligands. However, the HeLa S3 cell line, which is insensitive to TNF-alpha, showed no growth inhibition even by combination treatment. Bestatin methyl ester, a more cell-permeable derivative of bestatin with similar inhibitory activity tocytosolic neutral aminopeptidase, potentiated cell growth inhibition of CH11 more efficiently than bestatin. Other cytosolic neutral aminopeptidase inhibitors such as actinonin and puromycin also augmented cell growth suppression by CH11, while an enantiomer of bestatin lacking aminopeptidase inhibitory action did not increase the growth-inhibitory effects of CH11. The combination of 10 mug/ml of bestatin with CH11 promoted processing of capase 3 to the active form p17 and efflux of mitochondrial cytochrome c into the cytosol more quickly and more intensely than CH11 alone. Inhibition of aminopeptidase was not involved in dATP- and cytochrome c-dependent caspase 3-activation in a cell-free system. Bestatin significantly augmented activation of caspase 8, which is upstream of cytochrome c efflux in the apoptosis cascade. These results suggested that intracellular neutral aminopeptidase might play an important role in Fas- or TNF-alpha -induced solid tumor cell apoptosis. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 03:30:36