Cytotoxic effects of alkylphosphocholines or alkylphosphocholine-liposomes and macrophages on tumor cells.
The influence of the alkylphosphocholines (APC) on macrophage activation to tumor cytotoxicity was investigated in vitro with both mouse peritoneal and rat liver macrophages. For this purpose the compounds were used either in micellar or in liposomal form. The cytotoxic effect of micellar or liposomal APC was increased with prolongation of the aliphatic chain and was reduced for the liposomal form. Peritoneal macrophages incubated with APC-liposomes gave a comparable cytotoxic effect on MethA cells to that of the free, highly toxic APC alone. These liposomes can activate rat liver macrophages (Kupffer cells) in vitro to a moderate tumor cytotoxicity on C26 colon carcinoma cells, while the micellar APC were toxic to macrophages. A significant release of NO-radicals from peritoneal macrophages was obtained with Liposomes but not with micellar lipid. The release of tumor necrosis factor (TNF) was stimulated by incubation with micellar or liposomal HPC. Whereas the micellar HPC was comparable to lipopolysaccharide (LPS) in TNF release stimulation, the HPC-liposomes caused a much higher release.
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
R
R
Zeisig
S
S
Jungmann
I
I
Fichtner
T
T
Daemen
D
D
Arndt
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008081:Liposomes / Q000633:toxicity*; D008099:Liver / Q000166:cytology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D008081:Liposomes; D008823:Micelles; D014409:Tumor Necrosis Factor-alpha; D010767:Phosphorylcholine; D009569:Nitric Oxide; C039128:miltefosine