Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor.
In this study, we demonstrated several mechanisms exploring the inhibitory effect of low-dose adenosine on lymphoma cell growth. Adenosine, a purine nucleoside present in plasma and other extracellular fluids, acts as a regulatory molecule, by binding to G-protein associated cell-surface receptors, A1, A2 and A3. Recently we showed that low-dose adenosine released by muscle cells, inhibits tumour cell growth and thus attributes to the rarity of muscle metastases. In the present work, a cytostatic effect of adenosine on the proliferation of the Nb2-11C rat lymphoma cell line was demonstrated. This effect was mediated through the induction of cell cycle arrest in the G0/G1 phase and by decreasing the telomeric signal in these cells. Adenosine was found to exert its antiproliferative effect mainly through binding to its A3 receptor. The cytostatic anticancer activity, mediated through the A3 adenosine receptor, turns it into a potential target for the development of anticancer therapies.
Fishman
P
P
Laboratory of Clinical and Tumor Immunology, The Felsenstein Medical Research Center, Tel-Aviv University, Rabin Medical Center, Petach-Tikva, Israel. pnina@mor-reseach.com
Bar-Yehuda
S
S
Ohana
G
G
Pathak
S
S
Wasserman
L
L
Barer
F
F
Multani
A S
AS
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis; D008223:Lymphoma / Q000473:pathology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D016615:Telomere / Q000737:chemistry; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D000241:Adenosine