Adenosine modulates cell proliferation in human colonic adenocarcinoma. I. Possible involvement of adenosine A1 receptor subtypes in HT29 cells.
Several lines of evidence suggest that extracellular adenosine interacting with specific cell surface receptors may influence cell growth and differentiation of cancer cells in culture. The data presented here demonstrate that various treatments of human colonic adenocarcinoma HT29 cells in the presence of exogenously added adenosine deaminase, which converts extracellular adenosine into inosine, resulted in a significant decrease of the proliferation. Cell growth inhibition was also observed in the presence of adenosine A1 receptor antagonists. These various treatments also induced a significant elevation of basal intracellular cAMP levels. This strongly indicated that extracellular adenosine was maintaining low intracellular cAMP levels in HT29 cells. A partial pharmacological characterization of the binding of the adenosine A1 receptor agonist [3H]CCPA (2-chloro-N6-cyclopentyl[2,3,4,5-(3)H]adenosine), and the adenosine A1 receptor antagonist [3H]DPCPX (cyclopentyl-1,3-dipropyl[2,3-(3)H]xanthine), to HT29 cells is also provided. Together the data support the idea that A1-adenosine receptors are expressed in HT29 cells and might mediate part of the above described effects of adenosine on cell proliferation.
Lelièvre
V
V
Laboratoire de Biologie des Interactions Cellulaires, CNRS UMR 6558, Université de Poitiers, France.
Muller
J M
JM
Falcón
J
J
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C058394:2-chloro-N(6)cyclopentyladenosine; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D000241:Adenosine