Influence of the tyrosine kinase inhibitors STI571 (Glivec), lavendustin A and genistein on human mast cell line (HMC-1(560)) activation

J Cell Biochem. 2008 Mar 1;103(4):1076-88. doi: 10.1002/jcb.21480.


The human mast cell line (HMC-1(560)) was used to study the effects of tyrosine kinase (TyrK) inhibition on histamine release in consequence of intracellular Ca2+ or pH changes. This is important since the TyrK inhibitor STI571 (Glivec) inhibits proliferation and induces apoptosis in HMC-1(560). HMC-1(560) cells have a mutation in c-kit, which leads to a permanent phosphorylation of the KIT protein and their ligand-independent proliferation. The TyrK inhibitors STI571, lavendustin A and genistein decrease spontaneous histamine release in 24-h pre-incubated cells. Results are compared with those of the mast cell stabiliser cromoglycic acid, which also drops spontaneous histamine release. When exocytosis is stimulated by alkalinisation, STI571 pre-incubated cells release more histamine than non-pre-incubated cells. Alkalinisation-induced histamine release reaches still higher levels in STI571 cells with activated protein kinase C (PKC) by PMA. We do not observe modifications on histamine release in cells, treated with PKC inhibitors (rottlerin, Gf109203 or Gö6976). Lavendustin A- and genistein 24-h incubated cells behave similar to STI571 cells, whereas cromoglycic acid does not show effects after stimulation with alkalinisation. Stimulation of exocytosis with the Ca2+ ionophore ionomycin does not modify histamine response in TyrK inhibited cells. Ca2+ and pH changes are observed after long-time incubation with STI571. Results show that pH is still higher in STI571 pre-incubated cells after alkalinisation with NH4Cl, whereas intracellular Ca2+ concentration remains stable. This work further strength the importance of pHi as a cell signal and suggest that STI571 has transduction pathways in common with other TyrKs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzamides
  • Calcium / physiology
  • Cell Line
  • Cell Proliferation / drug effects
  • Enzyme Activation
  • Exocytosis
  • Genistein / pharmacology*
  • Histamine Release / drug effects*
  • Humans
  • Imatinib Mesylate
  • Mast Cells / drug effects*
  • Mast Cells / physiology
  • Phenols / pharmacology*
  • Piperazines / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / pharmacology*
  • Signal Transduction


  • Benzamides
  • Phenols
  • Piperazines
  • Pyrimidines
  • lavendustin A
  • Imatinib Mesylate
  • Genistein
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Calcium