The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism.

Abstract : Marine environment has frequently afforded a variety of biologically active compounds with strong anticancer and cytotoxic properties. In the present study, the mechanism of action of Jaspine B, an anhydrophytosphingosine derivative isolated from the marine sponge Jaspis sp., was investigated. Jaspine B was able to dose- and time-dependently decrease the viability of murine B16 and human SK-Mel28 melanoma cells. On these cells, Jaspine B treatment triggered cell death by typical apoptosis as illustrated by phosphatidylserine externalization, the release of cytochrome c and caspase processing. These effects were associated with increased intracellular ceramide levels owing to perturbed ceramide metabolism. Indeed, Jaspine B exposure strongly inhibited the activity of sphingomyelin synthase (SMS), an enzyme that converts de novo ceramide into the membrane lipid sphingomyelin. Moreover, whereas Jaspine B-induced cell death was enhanced in SMS1-depleted cells, it was strongly inhibited in cells that stably overexpress human SMS1. Finally, the cytotoxic effects of Jaspine B truncated analogs were also shown to be dependent on SMS activity. Altogether, Jaspine B is able to kill melanoma cells by acting on SMS activity and consequently on ceramide formation, and may represent a new class of cytotoxic compounds with potential applications in anticancer melanoma therapy.
Type de document :
Article dans une revue
Biochemical Pharmacology / Biochemistry and Pharmacology, 2009, 78 (5), pp.477-85. 〈10.1016/j.bcp.2009.05.002〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00409927
Contributeur : Marie Francoise Simon <>
Soumis le : vendredi 14 août 2009 - 09:49:56
Dernière modification le : jeudi 11 janvier 2018 - 06:15:23

Identifiants

Collections

Citation

Yahya Salma, Elodie Lafont, Nicole Therville, Stéphane Carpentier, Marie-José Bonnafé, et al.. The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism.. Biochemical Pharmacology / Biochemistry and Pharmacology, 2009, 78 (5), pp.477-85. 〈10.1016/j.bcp.2009.05.002〉. 〈inserm-00409927〉

Partager

Métriques

Consultations de la notice

55