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Titolo:
Activation of the Fas pathway independently of Fas ligand during apoptosisinduced by camptothecin in p53 mutant human colon carcinoma cells
Autore:
Shao, RG; Cao, CX; Nieves-Neira, W; Dimanche-Boitrel, MT; Solary, E; Pommier, Y;
Indirizzi:
NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA Fac Med & Pharm Dijon, INSERM U517, Dept Biol & Therapy Canc, Dijon, France Fac Med & Pharm Dijon Dijon France t Biol & Therapy Canc, Dijon, France
Titolo Testata:
ONCOGENE
fascicolo: 15, volume: 20, anno: 2001,
pagine: 1852 - 1859
SICI:
0950-9232(20010405)20:15<1852:AOTFPI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG-INDUCED APOPTOSIS; CANCER-CELLS; TOPOISOMERASE-I; LEUKEMIA-CELLS; DNA-DAMAGE; CUTTING EDGE; WILD-TYPE; DEATH; CD95; CYTOTOXICITY;
Keywords:
Bar; caspase; FADD; z-VAD; nuclease; programmed cell death;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Pommier, Y NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 4E28, Bethesda, MD 20892 USA NCI Bldg 37,Rm 4E28 Bethesda MD USA 20892 ethesda, MD 20892 USA
Citazione:
R.G. Shao et al., "Activation of the Fas pathway independently of Fas ligand during apoptosisinduced by camptothecin in p53 mutant human colon carcinoma cells", ONCOGENE, 20(15), 2001, pp. 1852-1859

Abstract

The present study explored the role of the cell surface receptor Fas (CD95/APO-1) in apoptosis induced by camptothecin (CPT) in the HT29 colon carcinoma cell line. CPT-induced apoptosis was associated with high molecular weight DNA fragmentation as measured by filter elution, This fragmentation wasinhibited by the caspase inhibitor, z-VAD-fmk and by cycloheximide, which also prevented proteolytic activation of caspase-3 and poly(ADP-ribose)polymerase cleavage. Under such conditions, Fas, Fas ligand, Bar, and p21 expression were increased and Fas recruited the FADD adaptor. Fas expression increase was blocked by cycloheximide but not by z-VAD-fmk, consistent with caspase activation downstream from Fas, Treatment of HT29 cells with Fast or with the CH-11 agonistic anti-Fas antibody potentiated the apoptotic response of cells treated with CPT, The anti-Fas blocking antibody ZB4 and the Fas-ligand inhibitor failed to protect HT29 cells from CPT-induced apoptosis,Such a protection was obtained by transient expression of constructs encoding a dominant-negative mutant of FADD, FADD in an antisense orientation and E8 or MC159 viral proteins that inhibit Fas-induced apoptosis at the level of FADD and procaspase-8, respectively. Together, these data show that topoisomerase I-mediated DNA damage-induced apoptosis involves activation of the Fas pathway without detectable Fas-ligand requirement in CPT-treated cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/10/20 alle ore 00:18:26