Amine oxidase-mediated cytotoxicity of spermine and epinephrine to human myelogenous leukemia K562 cells.
The effects of spermine and beta-adrenoceptor agonists (epinephrine, terbutaline and orciprenaline) in the presence and in the absence of fetal bovine serum (FBS) on human myelogenous leukemia K562 cells viability (V) and survival (N/Nc) were examined. Spermine-FBS significantly decreased both V and N/Nc of K562 cells. Aminoguanidine (AG), an amine oxidase inhibitor, and reduced form of glutathione abolished this effect demonstrating that the spermine-FBS action was amine oxidase-mediated. Epinephrine expressed a strong cytotoxicity to K562 cells which was abolished by pargyline, a specific monoamine oxidase (MAO) inhibitor, as well as by reduced form of glutathione. Terbutaline and orciprenaline exerted no cytotoxic activity to K562 cells cultured in FBS-supplemented medium, independently on the presence of spermine. However, terbutaline at concentrations of over 1 mmol strongly inhibited the cytotoxic effect on spermine-FBS. The relationship between cytotoxicity and chemical structure of beta-adrenoceptor agonists was discussed especially with respect to their stability toward oxidation.
Juranić
Z
Z
Institute for Oncology and Radiology, University of Belgrade, Serbia.
Joksimović
J
J
Spuzić
I
I
Juranić
I
I
Kidrić
M
M
D006631:Amine Oxidase (Copper-Containing); D002470:Cell Survival / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000502:physiology*; D013096:Spermine / Q000494:pharmacology*; D013726:Terbutaline / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013096:Spermine; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D013726:Terbutaline; D004837:Epinephrine