Sakaki Hirotsugu, Okada Masashi, Kuramoto Kenta, Takeda Hiroyuki, Watarai Hikaru, Suzuki Shuhei, Seino Shizuka, Seino Manabu, Ohta Tsuyoshi, Nagase Satoru, Kurachi Hirohisa, Kitanaka Chifumi
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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.
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.
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.
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.
背景/目的：组蛋白H3赖氨酸27位点三甲基化（H3K27me3）在全球范围内的增加与正常干细胞和癌细胞的分化有关，然而，H3K27me3在癌症干细胞（CSCs）调控中的作用仍知之甚少。我们使用选择性H3K27去甲基化酶抑制剂GSKJ4研究了H3K27me3增加对CSCs的影响。
检测了GSKJ4对源自A2780人卵巢癌细胞系的CSCs的活力、自我更新能力和肿瘤起始能力的影响。
GSKJ4在对正常人成纤维细胞无毒的浓度下诱导A2780 CSCs细胞死亡。GSKJ4还导致在GSKJ4处理后存活的A2780 CSCs的自我更新能力和肿瘤起始能力丧失。
我们的研究结果表明，H3K27甲基化可能在CSCs的维持中起抑制作用，并且GSKJ4可能代表一类新型的靶向CSCs的药物。
