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

Anticancer Res. 1988 Nov-Dec;8(6):1275-8.

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.

MeSH terms

  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biological Transport
  • Cell Line
  • Kinetics
  • Liposomes / administration & dosage*
  • Mice
  • Neoplasms, Experimental / metabolism*
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Liposomes
  • Organoplatinum Compounds
  • dichlorobis(cyclopentylamine)platinum
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases