title: Growth inhibitory effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine.
abstract: The growth inhibitory effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) and various liposome compositions of ET-18-OCH3 were compared in a standardized growth inhibition assay utilizing a diverse tumor cell line panel including cell lines expressing multidrug resistance. ET-18-OCH3 and ELL-12 (4:3:1:2, dioleoylphosphatidylcholine/ cholesterol/dioleoylphosphatidylethanolamine-glutaric acid/ET-18-OCH3), an optimal liposomal ET-18-OCH3 formulation, inhibited growth in the micromolar range in drug-sensitive and -resistant cells. In general, ET-18-OCH3-liposomes were about twofold less growth inhibitory than ET-18-OCH3. However, the known hemolytic effects of ET-18-OCH3 were greatly reduced, up to 20 or more times, by liposome association. The effects of ET-18-OCH3 and ELL-12 were compared in intracellular [Ca2+] modulation and DNA fragmentation assays. ET-18-OCH3 elicited both concentration- and serum-dependent transient and permanent increases in intracellular [Ca2+]. In contrast, ELL-12 did not modulate intracellular [Ca2+]. ET-18-OCH3 and ELL-12 similarly affected DNA fragmentation, which may be indicative of apoptosis. The results suggest that, although the specific growth inhibitory effects of ET-18-OCH3 and ELL-12 are similar, associating ET-18-OCH3 with stable well-characterized liposomes eliminates nonspecific cell membrane-associated lytic effects.
authors.affiliation: Liposome Company, Inc., Princeton, New Jersey 08540, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Peters
authors.forename: I
authors.initials: I
authors.lastname: Ahmad
authors.forename: A S
authors.initials: AS
authors.lastname: Janoff
authors.forename: M Y
authors.initials: MY
authors.lastname: Pushkareva
authors.forename: E
authors.initials: E
authors.lastname: Mayhew
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010742:Phospholipid Ethers / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D008081:Liposomes; D010742:Phospholipid Ethers; C026659:edelfosine; D002118:Calcium