Article (Scientific journals)
Mechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity.
Fillet, Marianne; Bentires-Alj, Mohamed; Deregowski, Valérie et al.
2003In Biochemical Pharmacology, 65 (10), p. 1633-42
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Keywords :
Apoptosis; caspase; ceramide; Caspase 3; Caspases/metabolism; Cell Survival/drug effects; Ceramides/pharmacology; Cytochrome c Group/metabolism; Enzyme Activation/drug effects; Enzyme Inhibitors/pharmacology; Humans; NF-kappa B/metabolism; Poly(ADP-ribose) Polymerases/metabolism; Sphingosine/analogs & derivatives/pharmacology; Tumor Cells, Cultured
Abstract :
[en] Ceramides are important intracellular second messengers that play a role in the regulation of cell growth, differentiation, and programmed cell death. To determine whether ceramides can mediate the apoptosis of HCT116 and OVCAR-3 cancer cells, exogenous C2-, C6-, and C16-ceramides were used to mimic the endogenous lipid increase that follows a large variety of stresses. C2- and C6-ceramides (cell-permeable ceramide analogs), but not C16-ceramide, induced nuclear factor-kappaB (NF-kappaB) DNA-binding, caspase-3 activation, poly(ADP-ribose) polymerase degradation, and mitochondrial cytochrome c release, indicating that apoptosis occurs through the caspase cascade and the mitochondrial pathway. No difference in survival was observed between control cells and cells expressing mutated IkappaBalpha and treated with the permeable ceramides. This suggests that, at least in these cell lines, stable NF-kappaB inhibition did not modify the ceramide-induced cytotoxicity pathway. C6-ceramide also induced a double block in G1 and G2, thus emptying the S phase.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Fillet, Marianne ;  Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Bentires-Alj, Mohamed;  Université de Liège - ULiège > Chimie Médicale
Deregowski, Valérie;  Université de Liège - ULiège > Chimie Médicale
Greimers, Roland ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Gielen, Jean-Louis ;  Université de Liège - ULiège > Chimie Médicale
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - GIGA-Research
Bours, Vincent ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Language :
English
Title :
Mechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity.
Publication date :
2003
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
65
Issue :
10
Pages :
1633-42
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FNRS; CAC
Available on ORBi :
since 06 August 2009

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