Sphingolipidomics of A2780 human ovarian carcinoma cells treated with synthetic retinoids.
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.
Valsecchi
Manuela
M
Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, 20090 Segrate, Italy.
Aureli
Massimo
M
Mauri
Laura
L
Illuzzi
Giuditta
G
Chigorno
Vanna
V
Prinetti
Alessandro
A
Sonnino
Sandro
S
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D017313:Fenretinide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D013107:Sphingolipids / Q000032:analysis*
C494898:4-oxofenretinide; D000970:Antineoplastic Agents; D013107:Sphingolipids; D017313:Fenretinide