title: GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Sakaki
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan ckitanak@med.id.yamagata-u.ac.jp m-okada@med.id.yamagata-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kuramoto
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Watarai
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Seino
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Seino
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan ckitanak@med.id.yamagata-u.ac.jp m-okada@med.id.yamagata-u.ac.jp.
authors.forename: Chifumi
authors.initials: C
authors.lastname: Kitanaka
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human
keywords: JMJD3; UTX; cancer treatment; epigenetic; histone modification; xenograft analysis