Induction of apoptosis in HL-60 human promyelocytic leukemia cells by adenosine A(3) receptor agonists.
The effects of adenosine (ADO) analogs on cells of the human promyelocytic HL-60 line were examined. ADO A(3) receptor agonists, N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA, 30-60 microM) and 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (CI-IB-MECA, 10-30 microM) induced apoptotic cell death. In contrast, neither an A(1)/A(2) antagonist (XAC) nor other selective ADO receptor agonists (CPA, NECA and CGS21680) induced apoptosis at concentrations of <30 microM. Both IB-MECA and CI-IB-MECA significantly induced Ca(2+) release from intracellular Ca(2+) pools followed by Ca(2+) influx, suggesting the presence of phospholipase C-coupled ADO A(3) receptors 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 A(3) receptors is responsible for the ADO-induced apoptosis in HL-60 cells and could be of potential therapeutic value in the treatment of leukemia.
Kohno
Y
Y
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sei
Y
Y
Koshiba
M
M
Kim
H O
HO
Jacobson
K A
KA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger / Q000032:analysis; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000502:physiology; D013329:Structure-Activity Relationship
D017931:DNA Primers; D004273:DNA, Neoplasm; D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine; D002118:Calcium