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Jaspine B induces nonapoptotic cell death in gastric cancer cells independently of its inhibition of ceramide synthase

AuthorsCingolani, Francesca; Simbari, Fabio CSIC; Abad, José Luis CSIC ORCID ; Casasampere, Mireia; Fabriàs, Gemma CSIC ORCID; Futerman, Anthony H.; Casas, Josefina CSIC ORCID
KeywordsAnticancer drugs
Liquid chromatography-mass spectrometry
Issue DateAug-2017
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Lipid Research 58 (8) 1500-1513 (2017)
AbstractSphingolipids (SLs) have been extensively investigated in biomedical research due to their role as bioactive molecules in cells. Here, we describe the effect of a SL analog, jaspine B (JB), a cyclic anhydrophytosphingosine found in marine sponges, on the gastric cancer cell line, HGC-27. JB induced alterations in the sphingolipidome, mainly the accumulation of dihydrosphingosine, sphingosine, and their phosphorylated forms due to inhibition of ceramide synthases. Moreover, JB provoked atypical cell death in HGC-27 cells, characterized by the formation of cytoplasmic vacuoles in a time and dose-dependent manner. Vacuoles appeared to originate from macropinocytosis and triggered cytoplasmic disruption. The pan-caspase inhibitor, z-VAD, did not alter either cytotoxicity or vacuole formation, suggesting that JB activates a caspase-independent cell death mechanism. The autophagy inhibitor, wortmannin, did not decrease JB-stimulated LC3-II accumulation. In addition, cell vacuolation induced by JB was characterized by single-membrane vacuoles, which are different from double-membrane autophagosomes. These findings suggest that JB-induced cell vacuolation is not related to autophagy and it is also independent of its action on SL metabolism. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
Publisher version (URL)10.1194/jlr.M072611
Appears in Collections:(IQAC) Artículos

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