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.
Jong-Eun Kim  1 ,  Sung-Young Lee  2 ,  Mi Jang  3 ,  Hyo-Kyung Choi  4 ,  Jong Hun Kim  5 ,  Hanyong Chen  6 ,  Tae-Gyu Lim  7 ,  Zigang Dong  8 ,  Ki Won Lee  9  10
Affiliations
  • 1. Research Institute of Biotechnology and Medical Converged Science, Dongguk University-Seoul, Goyang 10326, Korea. [email protected].
  • 2. The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. [email protected].
  • 3. Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. [email protected].
  • 4. Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. [email protected].
  • 5. Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. [email protected].
  • 6. The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. [email protected].
  • 7. Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. [email protected].
  • 8. The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. [email protected].
  • 9. Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. [email protected].
  • 10. Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. [email protected].
PMID: 29064398 DOI: 10.3390/ijms18102228
Abstract

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.
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