Identification of 4′-O-β-D-glucosyl-5-O-methylvisamminol as a novel epigenetic suppressor of histone H3 phosphorylation at Ser10 and its interaction with 14-3-3ε

被引:6
|
作者
Kang, Jong-Su [1 ]
Chin, Young-Won [1 ]
Lee, Kyeong [1 ]
Kim, Young-Woo [1 ]
Choi, Bu Young [2 ]
Keum, Young-Sam [1 ]
机构
[1] Dongguk Univ, Coll Pharm, Goyang 410773, Gyeonggi Do, South Korea
[2] Seowon Univ, Dept Phamaceut Sci & Engn, Cheongju 361742, Chungbuk, South Korea
关键词
4 '-O-beta-D-Glucosyl-5-O-methylvisamminol; Histone phosphorylation; 14-3-3; epsilon; Aurora B kinase; 14-3-3; PROTEINS; CANCER;
D O I
10.1016/j.bmcl.2014.07.005
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Natural compounds are regarded as a rich source for potential anti-inflammatory and anti-carcinogenic agents. Increasing evidence indicates that histone phosphorylation at Ser10 is a marker for cell cycle progression during the mitosis and the induction of immediate pro-inflammatory genes during the interphase. In the present study, we have screened our in-house natural compounds to find out new chemical inhibitor(s) of histone H3 phosphorylation at Ser10. As a result, we observed that alpha-amyrin, oleanolic acid, marliolide, and 4'-O-beta-D-glucosyl-5-O-methylvisamminol decreased the levels of histone H3 phosphorylation at Ser10 and c-Jun. In particular, we observed that 4'-O-beta-D-glucosyl-5-O-methylvisamminol suppressed the direct interaction of histone H3 with 14-3-3 epsilon, inhibited the aurora B kinase activity and delayed the mitotic cell cycle progression. We reports 4'-0-beta-D-glucosyl-5-O-methylvisamminol as the first epigenetic natural chemical inhibitor that can abrogates the mitotic cell cycle progression and immediate pro-inflammatory gene expressions via suppression of histone H3 phosphorylation at Ser10 and its interaction with 14-3-3 epsilon. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4763 / 4767
页数:5
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