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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal carcinoma cells treated with doxorubicin combined with a farnesyl-transferase inhibitor
Biochemical Pharmacology, Volume 65, No. 3, Year 2003
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Description
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more sensitive to chemotherapy than other head and neck carcinomas. Spectacular regressions are frequently observed after induction chemotherapy. However, these favorable responses are difficult to predict and often of short duration. So far there have been only few experiments to investigate the mechanisms which underline the cytotoxic effects of anti-neoplastic drugs against NPC cells. In addition, these studies were performed almost entirely on EBV-negative cell lines therefore not truly representative of NPC cells. For the first time, we have used two EBV-positive NPC tumor lines derived from a North African (C15) and a Chinese (C666-1) patient as in vitro targets for a panel of anti-neoplastic agents. Doxorubicin, taxol and in a lesser extent cis-platinum efficiently inhibited NPC cell proliferation at clinically relevant concentrations, but all three agents failed to induce apoptosis. However, massive apoptosis of C15 cells was achieved when doxorubicin (1μM) was combined with a farnesyl-transferase inhibitor, BIM 2001 (5μM). Moreover, this apoptotic process was associated with a caspase-dependent early cleavage of the TNF-receptor associated factor 1 (TRAF-1) molecule, a signaling adaptor which is specifically expressed in latently EBV-infected cells. TRAF-1 cleavage might become a useful indicator of chemo-induced apoptosis in EBV-associated NPCs. © 2002 Elsevier Science Inc. All rights reserved.
Authors & Co-Authors
Vicat, Jean Michel
France, Villejuif
Institut de Cancerologie Gustave Roussy
Ardila-Osorio, Hector
France, Villejuif
Institut de Cancerologie Gustave Roussy
Khabir, Abdelmajid
Tunisia, Sfax
Chu Habib Bourguiba
Brezak, Marie Christine
France, Les Ulis
Institut Henri Beaufour
Viossat, Isabelle
France, Les Ulis
Institut Henri Beaufour
Kasprzyk, Philip
United States, Milford
Biomeasure, Inc.
Jlidi, Rachid
Tunisia, Sfax
Chu Habib Bourguiba
Opolon, Paule
France, Villejuif
Institut de Cancerologie Gustave Roussy
Ooka, Tadamassa
France, Lyon
Virologie et Pathologie Humaine
Prevost, Grégoire
France, Les Ulis
Institut Henri Beaufour
Huang, Dolly P.
Hong Kong
Prince of Wales Hospital Hong Kong
Busson, Pierre
France, Villejuif
Institut de Cancerologie Gustave Roussy
Statistics
Citations: 15
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1016/S0006-2952(02)01449-1
ISSN:
00062952
Research Areas
Cancer
Health System And Policy