Hirotsugu Sakaki1, Masashi Okada2, Kenta Kuramoto3, Hiroyuki Takeda4, Hikaru Watarai5, Shuhei Suzuki4, Shizuka Seino6, Manabu Seino1, Tsuyoshi Ohta7, Satoru Nagase7, Hirohisa Kurachi8, Chifumi Kitanaka9. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 2. 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. 3. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan. 4. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan. 5. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan. 6. 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. 7. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 8. 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. 9. 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.
Abstract
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. Copyright
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 humanovarian 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. Copyright
Authors: Allie Y Chen; Rebecca N Adamek; Benjamin L Dick; Cy V Credille; Christine N Morrison; Seth M Cohen Journal: Chem Rev Date: 2018-09-07 Impact factor: 60.622
Authors: Xiaoyan Xu; Jianjun Wang; Chen Yan; Yingli Men; Huang Jiang; Huijuan Fang; Xianwei Xu; Jinhua Yang Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2020-11-30