Reference : Mechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity.
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
Mechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity.
Fillet, Marianne mailto [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]
Bentires-Alj, Mohamed [Université de Liège > Chimie Médicale > > >]
Deregowski, Valérie [Université de Liège > Chimie Médicale > > >]
Greimers, Roland mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Gielen, Jean-Louis mailto [Université de Liège > Chimie Médicale > > >]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - GIGA-Research >]
Bours, Vincent mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Merville, Marie-Paule [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Biochemical Pharmacology
Elsevier Science
Yes (verified by ORBi)
United Kingdom
[en] 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
[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.
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