Inhibitory effects of theophylline and dibutyryl cAMP on murine erythroleukemia cell differentiation.
Murine erythroleukemia cells can be induced to differentiate by a variety of compounds. We have previously shown that 5'-methylthioadenosine, an inhibitor of cAMP phosphodiesterase, blocks induction of these cells. The present study demonstrates that theophylline, another cAMP phosphodiesterase inhibitor, also blocks murine erythroleukemia cell differentiation in a concentration-dependent manner. Northern blot analysis indicates that this agent inhibits accumulation of alpha- and beta-globin transcripts. These findings are extended by demonstrating that dibutyryl cAMP exerts similar effects. Furthermore, theophylline and dibutyryl cAMP are synergistic in inhibiting appearance of the mature erythroid phenotype. The results thus suggest that cAMP regulates induction of murine erythroleukemia cell differentiation.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004920:Erythropoiesis / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D013806:Theophylline / Q000494:pharmacology*
D006454:Hemoglobins; D002110:Caffeine; D006418:Heme; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D004121:Dimethyl Sulfoxide