Proliferation of nontransformed cells is inhibited by adenosine metabolite of but not by parental 8-Cl-cyclic AMP.
In this study we evaluated the regulatory effect of 8-Cl-cyclic AMP (cAMP) on the proliferation of nontransformed cells. Our data indicate that similar to the reported inhibitory effect of 8-Cl-cAMP on the proliferation of Molt-4 lymphoma cells, the inhibitory effect of 8-Cl-cAMP on the proliferation of nontransformed fibroblast, myoblast and endothelial cells was dependent on serum or cyclic nucleotide phosphodiesterases and other nucleotide phosphatases. This suggested that the metabolism of 8-Cl-cAMP was required for the inhibition of cell proliferation. In addition, this serum-dependent inhibitory effect of 8-Cl-cAMP was antagonized by the presence of exogenous adenosine deaminase, suggesting that 8-Cl-adenosine was responsible for mediating the serum-dependent inhibitory effect of 8-Cl-cAMP on these cells. This idea was supported further by the ability of 8-Cl-adenosine to duplicate the inhibitory effect of 8-Cl-cAMP on cell proliferation in defined medium.
Division of Biology and Medicine, Brown University, Providence, Rhode Island.
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Han
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Chatterjee
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Wyche
D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D001769:Blood; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D051381:Rats
D015762:2-Chloroadenosine; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000243:Adenosine Deaminase; C075440:8-chloroadenosine