Sphingolipidomics of A2780 human ovarian carcinoma cells treated with synthetic retinoids

Manuela Valsecchi; Massimo Aureli; Laura Mauri; Giuditta Illuzzi; Vanna Chigorno; Alessandro Prinetti; Sandro Sonnino

Journal of Lipid Research (Jul 2010)

Sphingolipidomics of A2780 human ovarian carcinoma cells treated with synthetic retinoids

Manuela Valsecchi,
Massimo Aureli,
Laura Mauri,
Giuditta Illuzzi,
Vanna Chigorno,
Alessandro Prinetti,
Sandro Sonnino

Affiliations

Manuela Valsecchi: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Massimo Aureli: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Laura Mauri: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Giuditta Illuzzi: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Vanna Chigorno: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Alessandro Prinetti: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy
Sandro Sonnino: To whom correspondence should be addressed; Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy

Journal volume & issue: Vol. 51, no. 7
pp. 1832 – 1840

Abstract

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The dihydroceramide, ceramide, sphingomyelin, lactosylceramide, and ganglioside species of A2780 human ovarian carcinoma cells treated with the synthetic retinoids N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) in culture were characterized by ESI-MS. We characterized 32 species of ceramide and dihydroceramide, 15 of sphingomyelin, 12 of lactosylceramide, 9 of ganglioside GM2, and 6 of ganglioside GM3 differing for the long-chain base and fatty acid structures. Our results indicated that treatment with both 4-HPR and 4-oxo-4-HPR led to a marked increase in dihydroceramide species, while only 4-oxo-4-HPR led to a minor increase of ceramide species. Dihydroceramides generated in A2780 cells in response to 4-HPR or 4-oxo-4-HPR differed for their fatty acid content, suggesting that the two drugs differentially affect the early steps of sphingolipid synthesis. Dihydroceramides produced upon treatments with the drugs were further used for the synthesis of complex dihydrosphingolipids, whose levels dramatically increased in drug-treated cells.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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