Cyclic AMP levels and cellular kinetics during maturation of human promyelocytic leukemia cells.
Differentiation of human promyelocytic leukemia cells (HL-60) in response to several classes of inducing agents is characterized by the sequential appearance of granulocytic or monocytic markers. Compounds that increase intracellular cAMP in HL-60 cells induce a program of maturation in which cells demonstrate early functional phagocytic properties. Cyclic nucleotide metabolism was studied during monocytic and granulocytic differentiation of the HL-60 cell line. In synchronous and nonsynchronous cell cultures, cyclic AMP levels were raised 300-fold or 25-fold in response to N6, O2-dibutyryl adenosine 3':5'-cyclic monophosphate or the combination of prostaglandin E2 and theophylline, respectively. No reproducible changes in intracellular adenosine 3':5'-cyclic monophosphate levels occurred in response to retinoic acid or dimethyl sulfoxide, suggesting that changes in adenosine 3':5'-cyclic monophosphate levels alone do not mediate cell maturation induced by these compounds. Agents that increased intracellular cyclic AMP in HL-60 cells slowed the progress through the S and G2-M phase of the cell cycle, whereas other agents such as dimethyl sulfoxide stimulated cells through this same period.
D003994:Bucladesine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000032:analysis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015232:Dinoprostone; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D011458:Prostaglandins E / Q000494:pharmacology; D011494:Protein Kinases / Q000032:analysis; D013806:Theophylline / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D011458:Prostaglandins E; D014212:Tretinoin; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D011494:Protein Kinases; D015232:Dinoprostone; D004121:Dimethyl Sulfoxide