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Titolo:
Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis
Autore:
Lacour, S; Hammann, A; Wotawa, A; Corcos, L; Solary, E; Dimanche-Boitrel, MT;
Indirizzi:
Fac Med & Pharm Dijon, INSERM U517, F-21033 Dijon, France Fac Med & Pharm Dijon Dijon France F-21033 M U517, F-21033 Dijon, France
Titolo Testata:
CANCER RESEARCH
fascicolo: 4, volume: 61, anno: 2001,
pagine: 1645 - 1651
SICI:
0008-5472(20010215)61:4<1645:AASTCT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRAIL-INDUCED APOPTOSIS; FLICE-INHIBITORY PROTEIN; NF-KAPPA-B; FADD-DEPENDENT APOPTOSIS; CANCER-CELLS; DEATH DOMAIN; RECEPTOR KILLER/DR5; SIGNALING COMPLEX; APO-2 LIGAND; IN-VIVO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Dimanche-Boitrel, MT Fac Med & Pharm Dijon, INSERM U517, 7 Blvd Jeanne Arc, F-21033 Dijon, France Fac Med & Pharm Dijon 7 Blvd Jeanne Arc Dijon France F-21033
Citazione:
S. Lacour et al., "Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis", CANCER RES, 61(4), 2001, pp. 1645-1651

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new cytokine that was proposed to specifically induce apoptosis of cancer cells. In tumor cells that are resistant to the cytokine, subtoxic concentrationsof chemotherapeutic drugs can restore the response to TRAIL. The present study further explores the mechanisms that determine tumor cell sensitivity to TRAIL by comparing four human colon carcinoma cell lines, We show that colon cancer cell sensitivity to TRAIL-induced apoptosis and cytotoxicity correlates with the expression of the death receptors TRAIL-RI and TRAIL-R2 at the cell surface, as determined by flow cytometry, whereas the two decoy receptors TRAIL-R3 and TRAIL-R4 can be detected only in permeabilized cells, Clinically relevant concentrations of cisplatin and doxorubicin sensitizethe most resistant colon cancer cell lines to TRAIL-induced cell death without modifying the expression nor the localization of TRAIL receptors in these cells, TRAIL induces the activation of procaspase-8 and triggers caspase-dependent apoptosis of colon cancer cells. Cytotoxic drugs loser the signaling threshold required for TRAIL-induced procaspase-8 activation. In turn, caspase-8 cleaves Bid, a BH3 domain-containing proapoptotic molecule of the Bcl-2 family, and activates effector caspases. Together, these data indicate that chemotherapeutic drugs sensitize colon tumor cells to TRAIL-mediated caspase-8 activation and apoptosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 14:18:33