1. Academic Validation
  2. Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor

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

Affiliations

  • 1 Research Institute of Biotechnology and Medical Converged Science, Dongguk University-Seoul, Goyang 10326, Korea. jekim14@dongguk.edu.
  • 2 The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. mbiotec@hotmail.com.
  • 3 Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. jangmi@kfri.re.kr.
  • 4 Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. chkyoung@kfri.re.kr.
  • 5 Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. rose-0@snu.ac.kr.
  • 6 The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. hchen@hi.umn.edu.
  • 7 Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea. tglim83@kfri.re.kr.
  • 8 The Hormel Institute, University of Minnesota, Minneapolis, MN 55912, USA. zgdong@hi.umn.edu.
  • 9 Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. kiwon@snu.ac.kr.
  • 10 Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. kiwon@snu.ac.kr.
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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