Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor

Int J Mol Sci. 2017 Oct 24;18(10):2228. doi: 10.3390/ijms18102228.


Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell growth. Haspin kinase was identified as a direct target protein of coumestrol using kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We observed haspin kinase overexpression as well as greater phosphorylation of histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells. Computer modeling using the Schrödinger Suite program identified the binding interface within the ATP binding site. These findings suggest that the anti-cancer effect of coumestrol is due to the direct targeting of haspin kinase. Coumestrol has considerable potential for further development as a novel anti-cancer agent.

Keywords: cancer; coumestrol; haspin kinase; histone H3.

MeSH terms

  • A549 Cells
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Coumestrol / pharmacology*
  • HCT116 Cells
  • Histones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Molecular Docking Simulation
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary


  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • HASPIN protein, human
  • Protein Serine-Threonine Kinases
  • Coumestrol