title: Lipid microsphere preparation of a lipophilic ceramide derivative suppresses colony formation in a murine experimental pulmonary metastasis model.
abstract: Ceramide is a well-known regulator of apoptosis and cell growth. In this study, we synthesized lipophilic ceramide derivatives to incorporate into lipid microspheres (LM) and their activity was evaluated in vivo. Cera 03, a lipophilic ceramide derivative synthesized from membrane-permeable C2-ceramide, caused potent growth inhibition and DNA fragmentation of Meth A-T tumor cells in vitro. Its potency was similar to that of C2-ceramide. Both compounds increased the proportion of apoptotic cells. Cera 02, the diacetylated form of natural ceramide (Cer), also suppressed in vitro cell growth with a similar or higher potency to that of Cer, but both were far less potent than C2-ceramide and Cera 03. LM containing Cera 03 (Lipo-Cera 03) could not totally prevent metastatic incidence of Meth A-T cells, but reduced pulmonary metastatic nodules in number. Intravenous injection of Lipo-Cera 03 (1 mg/kg of Cera 03) produced about 35% inhibition, while Lipo-Cera 02 had no significant effect. In conclusion, Lipo-Cera 03 may have potential as an antimetastatic drug and may also be a useful tool for researching the role of ceramides in vivo.
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan. m2take@marianna-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takenaga
authors.forename: R
authors.initials: R
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: J
authors.initials: J
authors.lastname: Takeuchi
authors.forename: N
authors.initials: N
authors.lastname: Mizushima
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Morizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000008:administration & dosage* / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D007202:Indicators and Reagents; D008055:Lipids; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009362:Neoplasm Metastasis / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D004337:Drug Carriers; D007202:Indicators and Reagents; D008055:Lipids