GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells.
GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells.
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发表时间：
2015-12
影响因子：
2
通讯作者：
Hirotsugu Sakaki;M. Okada;Kenta Kuramoto;Hiroyuki Takeda;Hikaru Watarai;Shuhei Suzuki;Shizuka Seino;Manabu Seino;T. Ohta;S. Nagase;H. Kurachi;C. Kitanaka
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文献类型：
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作者：
Hirotsugu Sakaki;M. Okada;Kenta Kuramoto;Hiroyuki Takeda;Hikaru Watarai;Shuhei Suzuki;Shizuka Seino;Manabu Seino;T. Ohta;S. Nagase;H. Kurachi;C. Kitanaka
背景/目的组蛋白H3赖氨酸27位三甲基化（H3 K27 me 3）的整体增加与正常干细胞和癌细胞的分化有关，然而H3 K27 me 3在控制癌干细胞（CSCs）中的作用仍知之甚少。我们使用选择性H3 K27脱甲基酶抑制剂GSKJ 4研究了H3 K27 me 3增加对CSC的影响。材料和方法检测GSKJ 4对来自A2780人卵巢癌细胞系的CSC的活力以及对CSC的自我更新和肿瘤起始能力的影响。结果GSKJ 4在对正常人成纤维细胞无毒的浓度下诱导A2780 CSC细胞死亡。GSKJ 4还导致GSKJ 4处理后存活的A2780 CSC的自我更新和肿瘤起始能力的丧失。结论H3 K27甲基化可能对CSC的维持具有抑制作用，GSKJ 4可能是一类新的CSC靶向药物。
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.