The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1

FEBS Lett. 2009 Aug 6;583(15):2540-6. doi: 10.1016/j.febslet.2009.07.017. Epub 2009 Jul 18.


Eosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Eosinophils / drug effects*
  • Eosinophils / physiology
  • Eosinophils / ultrastructure
  • Humans
  • Membrane Potential, Mitochondrial / physiology
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Purines / pharmacology*
  • Roscovitine


  • Caspase Inhibitors
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Purines
  • Roscovitine
  • Cyclin-Dependent Kinases
  • Caspases