Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation

Eur J Pharmacol. 1998 May 29;350(1):121-7. doi: 10.1016/s0014-2999(98)00227-1.


The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H2 receptors showed a rapid, homologous desensitization, which might explain the dissimilar responses to histamine and dbcAMP. Forskolin induced an increase in cAMP levels in a concentration-dependent manner (EC50=30 microM) for an extended period of at least 24 h. Forskolin but not histamine (up to 100 microM), also inhibited cell growth in a dose-dependent fashion (EC50=22 microM). After 3 days of incubation, 75 microM forskolin induced U937 cell differentiation as judged by an increased rate of reduction of nitrobluetetrazolium (mean+/-S.E.M.: 21.3+/-6.6% in treated cells vs. 3.2+/-1.9% in the control group, P < 0.001) and an augmented chemotactic response to complement 5a (C5a) (33.2+/-5.9% in forskolin-treated vs. 0.34+/-0.12% in control cells, P < 0.01). Furthermore, c-Myc levels decreased following forskolin treatment, while the histamine H2 receptor agonist dimaprit had no effect. We conclude that forskolin induces U937 cell differentiation through a sustained rise in cAMP levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Cell Line
  • Chemotaxis / drug effects
  • Colforsin / pharmacology*
  • Cyclic AMP / metabolism*
  • Dose-Response Relationship, Drug
  • Genes, myc / drug effects
  • Genes, myc / physiology
  • Histamine / metabolism
  • Humans
  • Oxidation-Reduction
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Colforsin
  • Histamine
  • Cyclic AMP