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

Abstract

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.