Inhibition of uridine transport through sarcoma-180 cell membrane by anthracycline antibiotics

Mechanism of Action of Alpha-Methylene-Gamma-Lactone Derivatives of Substituted Nucleic Acid Bases in Tumour Cells

“…Data presented in table 2 show that the 3H-uridine uptake by sarcoma-180 cells at 20°C is significantly inhibited by the derivatives 1, 4 and 7 but not by 10. It is known that, at low temperature, cells take up nucleosides from the medium and me tabolise them to nucleotides, with a much reduced incorporation rate into nucleic acid [13,14], Under the experimental con ditions used in the present experiments, the uptake of 3H-uridine by sarcoma-180 cells was almost linear up to 1 h, and the incorporation of uridine into an acid-in soluble fraction was less than 5% of that into a whole cell at 20°C [12], Mammalian cells take up nucleosides from the environ ment by simple diffusion, which is signifi cant only at relatively high concentrations of nucleosides, while at low concentra tions carrier-mediated transport is the main pathway [13][14][15][16][17], At the concentra tion used in the present study, carrier-me diated transport is the principal pathway of uridine uptake. It appears from our re sults that antitumour activities of the com pounds 1, 4 and 7 are mediated primarily through inhibition in the carrier-mediated active transport of small molecules through tumour cell membranes.…”

“…The uptake of uridine into sarcoma-180 cells in the presence of lactone derivatives was studied ac cording to the method of Roychoudhury et al [12], Sarcoma-180 cells (2x 106 cells/ml) were incubated at 20°C with gentle shaking in Medium 199 with Earle's salt, pH 7.4, with 'H-uridine (16.36 pCi/ml). The derivatives were added to one group at a concen tration of 200 pg/ml while another was treated as control (in the presence of an equal volume of sol vent).…”

Adriamycin inhibits PTH-mediated but not PGE2-mediated stimulation of cyclic AMP formation in isolated bone cells

“…Adriamycin was also found to be a specific inhibitor of Na+/Ca 2+ exchange in heart vesicles [19]. A low concentration (10 p~g/ml) has been shown to cause a noncompetitive inhibition of uridine transport in sarcoma 180 cells within 30 min [20]. These effects appear to stem from a direct interaction between adriamycin and phospholipid components of the plasma membrane.…”