title: Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells.
abstract: The cytotoxic effects of N-acetylsphingosine (C2-Cer) and N-hexanoylsphingosine (C6-Cer) were compared together with their specific intracellular accumulation profiles and metabolism in human CHP-100 neuroepithelioma cells. The two short-chain ceramides, administered in the culture medium at an equimolar concentration, evoked a differential apoptotic response, with C6-Cer showing markedly more cytotoxic than C2-Cer. Apoptosis, that was suppressed in both cases by inhibition of caspase-9, but not of caspase-8, associated with a higher intracellular accumulation of C6-Cer over C2-Cer, notwithstanding C6-Cer was actively metabolized by direct glucosylation or by conversion to natural ceramide via the sphingosine salvage pathway, whereas C2-Cer was apparently metabolically inhert. C2-Cer cytotoxicity was markedly enhanced by increasing its concentration in the culture medium, and this response associated with a higher intracellular accumulation of this compound, in the absence of any natural ceramide elevation. These results support the notion that the differential apoptotic effect evoked by C2-Cer and C6-Cer in CHP-100 cells is driven by their differential intracellular accumulation profiles, but not by their differential property to generate natural ceramide via the sphingosine salvage pathway.
authors: Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
authors: Sabrina
authors: S
authors: Di Bartolomeo
authors: Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
authors: Antonio
authors: A
authors: Agostini
authors: Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy. Electronic address: spinedi@uniroma2.it.
authors: Angelo
authors: A
authors: Spinedi
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D018302:Neoplasms, Neuroepithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D046569:Neuroepithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; C064769:N-acetylsphingosine; C101954:N-caproylsphingosine; D013110:Sphingosine
keywords: Apoptosis; Long-chain ceramide; N-acetylsphingosine; N-hexanoylsphingosine; Sphingosine salvage pathway