title: Incorporation of cis-dichlorobiscyclopentylamineplatinum (II) into liposomes enhances its uptake by ADJ/PC6A tumour cells: comparative effects of the free and liposome-incorporated drug on the cyclic 3'-5' nucleotide phosphodiesterase activity.
abstract: ADJ/PC6A tumour cells in tissue culture can incorporate large amounts of 14C-cholesterol-labeled liposomes prepared by phosphatidylcholine: cholesterol: phosphatidic acid (7:2:1 molar proportions) without cytotoxic effects. Fusion of liposomes with the cell plasma membrane may represent an important pathway for lipid incorporation. The incorporation of the antitumour drug cis-dichlorobiscyclopentylamineplatinum (II) in these liposomes greatly enhances its cytotoxicity against ADJ/PC6A tumour cells. Cis-dichlorobiscyclopentylamineplatinum (II) incorporate into liposomes caused a two-fold elevation of cyclic AMP as compared to the free drug in ADJ/PC6A tumour cells, 24 h after treatment with a dose of 0.2 micrograms/ml. Liposomes containing cis-dichlorobiscyclopentylamineplatinum (II) at concentrations as low as 0.6 micrograms/ml effectively inhibited (approximately 70%) the activity of cyclic AMP-phosphodiesterase, which was used as functional parameter in this study. Similar inhibition of the enzyme activity by the free drug was achieved only at concentrations as high as 5 micrograms/ml. It is suggested that the incorporation of cis-dichlorobiscyclopentylamineplatinum (II) into liposomes offers a potentially useful tool for enhancing the cytotoxicity of the drug.
authors.affiliation: Department of Experimental Physiology, University of Athens Medical School, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Deliconstantinos
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002460:Cell Line; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C011764:dichlorobis(cyclopentylamine)platinum; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases