Lipid microsphere preparation of a lipophilic ceramide derivative suppresses colony formation in a murine experimental pulmonary metastasis model

Ceramide is a well-known regulator of apoptosis and cell growth. In this st udy, we synthesized lipophilic ceramide derivatives to incorporate into lip id microspheres (LM) and their activity was evaluated in vivo. Cera 03, a lipophilic ceramide derivative synthesized from membrane-permeab le C-2-ceramide, caused potent growth inhibition and DNA fragmentation of M eth A-T tumor cells ill vitro. Its potency was similar to that of C-2-ceram ide. Both compounds increased the proportion of apoptotic cells, Cera 02, t he diacetylated form of natural ceramide (Cer), also suppressed in vitro ce ll growth with a similar or higher potency to that of Cer, but both were fa r less potent than C-2-ceramide and Cera 03. LM containing Cera 03 (Lipo-Cera 03) could not totally prevent metastatic i ncidence of Meth A-T cells, but reduced pulmonary metastatic nodules in num ber. Intravenous injection of Lipo-Cera 03 (1 mg/kg of Cera 03) produced ab out 35% inhibition, while Lipo-Cera 02 had no significant effect, In conclusion, Lipo-Cera 03 may have potential as an antimetastatic drug an d may also be a useful tool for researching the role of ceramides in vivo.