GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells

Anticancer Res. 2015 Dec;35(12):6607-14.


Background/aim: Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of cancer stem cells (CSCs) remains poorly understood. We investigated the impact of increased H3K27me3 on CSCs using a selective H3K27 demethylase inhibitor GSKJ4.

Materials and methods: The effect of GSKJ4 on the viability as well as on the self-renewal and tumor-initiating capacity of CSCs derived from the A2780 human ovarian cancer cell line was examined.

Results: GSKJ4 induced cell death in A2780 CSCs at a concentration non-toxic to normal human fibroblasts. GSKJ4 also caused loss of self-renewal and tumor-initiating capacity of A2780 CSCs surviving GSKJ4 treatment.

Conclusion: Our findings suggest that H3K27 methylation may have an inhibitory role in the maintenance of CSCs and that GSKJ4 may represent a novel class of CSC-targeting agents.

Keywords: JMJD3; UTX; cancer treatment; epigenetic; histone modification; xenograft analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Disease Models, Animal
  • Female
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / metabolism*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Xenograft Model Antitumor Assays


  • Jumonji Domain-Containing Histone Demethylases
  • KDM6B protein, human