title: Complexation of c6-ceramide with cholesteryl phosphocholine - a potent solvent-free ceramide delivery formulation for cells in culture.
abstract: Ceramides are potent bioactive molecules in cells. However, they are very hydrophobic molecules, and difficult to deliver efficiently to cells. We have made fluid bilayers from a short-chain D-erythro-ceramide (C6-Cer) and cholesteryl phosphocholine (CholPC), and have used this as a formulation to deliver ceramide to cells. C6-Cer complexed with CholPC led to much larger biological effects in cultured cells (rat thyroid FRTL-5 and human HeLa cells in culture) compared to C6-Cer dissolved in dimethyl sulfoxide (DMSO). Inhibition of cell proliferation and induction of apoptosis was significantly more efficient by C6-Cer/CholPC compared to C6-Cer dissolved in DMSO. C6-Cer/CholPC also permeated cell membranes and caused mitochondrial Ca(2+) influx more efficiently than C6-Cer in DMSO. Even though CholPC was taken up by cells to some extent (from C6-Cer/CholPC bilayers), and was partially hydrolyzed to free cholesterol (about 9%), none of the antiproliferative effects were due to CholPC or excess cholesterol. The ceramide effect was not limited to D-erythro-C6-Cer, since L-erythro-C6-Cer and D-erythro-C6-dihydroCer also inhibited cell priolifereation and affected Ca(2+) homeostasis. We conclude that C6-Cer complexed to CholPC increased the bioavailability of the short-chain ceramide for cells, and potentiated its effects in comparison to solvent-dissolved C6-Cer. This new ceramide formulation appears to be superior to previous solvent delivery approaches, and may even be useful with longer-chain ceramides.
authors.affiliation: Cell Biology, Åbo Akademi University, Turku, Finland.
authors.forename: Pramod
authors.initials: P
authors.lastname: Sukumaran
authors.forename: Max
authors.initials: M
authors.lastname: Lönnfors
authors.forename: Otto
authors.initials: O
authors.lastname: Långvik
authors.forename: Ilari
authors.initials: I
authors.lastname: Pulli
authors.forename: Kid
authors.initials: K
authors.lastname: Törnquist
authors.forename: J Peter
authors.initials: JP
authors.lastname: Slotte
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D012997:Solvents / Q000737:chemistry; D014316:Tritium / Q000378:metabolism
chemical_list: D002518:Ceramides; C492068:N-hexanoyldihydrosphingosine; D012997:Solvents; C101954:N-caproylsphingosine; D014316:Tritium; D010767:Phosphorylcholine; D002118:Calcium; D004121:Dimethyl Sulfoxide