Adenosine contributes to the amine oxidase-mediated spermine cytotoxicity to human myelogenous leukemia K562 cells.
The effects of adenosine, aminophylline, dipyridamole and salbutamol on the amine oxidase-mediated spermine cytotoxicity to KS62 human myelogenous leukemia cells without Ph-chromosome, spontaneously enriched with mildly adherent cells, were studied. In the absence of spermine, adenosine expressed very mild inhibitory action on K562 cell survival, while in combination with the polyamine an almost additive increase in spermine-FBS cytotoxicity was observed. Aminophylline and salbutamol attenuated both spermine-FBS and spermine-FBS-adenosine suppression of cell survival and viability when equimolar concentration of these agents and the adenosine were applied. Pre-treatment of the cells with higher adenosine levels, in the presence of either aminophylline or dipyridamole, or salbutamol, was associated with decreased K562 cell survival, with the appearance of morphological changes in 10-20% of cells. Additional spermine-FBS cytotoxic effect was not observed in cells pre-treated with adenosine-aminophylline, or adenosine-salbutamole, but morphological changes in 10-20% of cells, even in the presence of spermine, was observed again. Dipyridamole alone suppressed very weakly K562 cell survival. In cells pretreated with dipyridamole, in the presence of spermine-FBS, an additive decrease in cell survival was observed. Pre-treatment of cells with dipyridamole and adenosine in presence of spermine-FBS did not result in a decrease of cell survival compared to the one obtained in dipyridamole-spermine-FBS treated cells.
Institute of Oncology and Radiology, Belgrade, Yugoslavia.
Z
Z
Juranić
J
J
Joksimović
S
S
Radulović
I
I
Juranić
D000241:Adenosine / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D014665:Vasodilator Agents; D000628:Aminophylline; D013096:Spermine; D004176:Dipyridamole; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000241:Adenosine; D000420:Albuterol