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Induction of Apoptosis in HL-60 Human Promyelocytic Leukemia Cells by Adenosine A3Receptor Agonists

https://doi.org/10.1006/bbrc.1996.0331Get rights and content

Abstract

The effects of adenosine (ADO) analogs on cells of the human promyelocytic HL-60 line were examined. ADO A3receptor agonists, N6-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide (IB-MECA, 30–60 μM) and 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide (CI-IB-MECA, 10–30 μM) induced apoptotic cell death. In contrast, neither an A1/A2antagonist (XAC) nor other selective ADO receptor agonists (CPA, NECA and CGS21680) induced apoptosis at concentrations of ≤30 μM. Both IB-MECA and CI-IB-MECA significantly induced Ca2+release from intracellular Ca2+pools followed by Ca2+influx, suggesting the presence of phospholipase C-coupled ADO A3receptors on HL-60 cells. This was further supported by the presence of mRNA of ADO A3 receptor in the cells. These results suggest that activation of ADO A3receptors is responsible for the ADO-induced apoptosis in HL-60 cells and could be of potential therapeutic value in the treatment of leukemia.

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Abbreviations used:ADO, adenosine; CADO, 2-chloroadenosine; CGS 21680, 2-[4-[(2-carboxyethyl)-phenyl]ethylamino]-5′N-ethylcarboxamidoadenosine; CI-IB-MECA, N6-(3-iodobenzyl)-2-chloro-adenosine-5′-N-methyluronamide; CPA, N6-cyclopentyladenosine; IB-MECA, N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide; NECA, 5′-N-ethylcarboxamidoadenosine; Tris, tris(hydroxymethyl)]aminomethane; XAC, (8-[4-[[[[(2-aminoethyl)amino]-carbonyl]methyl]oxy]phenyl]-1,3-dipropylxanthine).

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