Forskolin potentiates G-CSF-induced proliferation of a murine myeloblastic leukemia cell line

Leuk Res. 1994 Feb;18(2):111-7. doi: 10.1016/0145-2126(94)90127-9.


The role of the cAMP/A-kinase signaling pathway in G-CSF dependent proliferation of murine myeloblastic NFS-60 cells was investigated. G-CSF treatment resulted in a rapid and transient elevation of cAMP content of NFS-60 cells. G-CSF treatment of NFS-60 cells also resulted in the activation of A-kinase parallel to the increase in cAMP concentration. A low concentration (0.2-10 nM) of forskolin augmented the G-CSF-dependent cell proliferation, although forskolin by itself had no effect on NFS-60 cell growth. Forskolin did not affect the IL-3-induced proliferation of this cell line. Addition of forskolin resulted in further increases in the cAMP level, activation of A-kinase in NFS-60 cells stimulated by G-CSF. Proliferation of NFS-60 cells by G-CSF, but not by IL-3, was blocked by the axial diastereoisomer of adenosine 3',5'-phosphorothioate (Rp-cAMPS), a competitive cAMP antagonist. KT-5720(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexyloxy-8-methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2,7b, 11a-triazadibenzo(a,g) cycloocta(c,d,e)trinden-1-one), an A-kinase inhibitor, inhibited the G-CSF-dependent proliferation. These findings suggest that activation of the cAMP/A-kinase signaling pathway may be involved in G-CSF-mediated cell proliferation of NFS-60 cells, whereas IL-3-dependent proliferation is not mediated in such a manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbazoles*
  • Cell Division / drug effects
  • Colforsin / pharmacology*
  • Cyclic AMP / metabolism
  • Cyclic AMP / physiology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Drug Synergism
  • Enzyme Activation
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Indoles / pharmacology
  • Interleukin-3 / pharmacology
  • Leukemia, Experimental / metabolism
  • Leukemia, Experimental / pathology*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Mice
  • Mice, Inbred DBA
  • Pyrroles / pharmacology
  • Signal Transduction
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology


  • Carbazoles
  • Indoles
  • Interleukin-3
  • Pyrroles
  • Granulocyte Colony-Stimulating Factor
  • Colforsin
  • KT 5720
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases