title: 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.
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 α-amyrin, oleanolic acid, marliolide, and 4'-O-β-D-glucosyl-5-O-methylvisamminol decreased the levels of histone H3 phosphorylation at Ser10 and c-Jun. In particular, we observed that 4'-O-β-D-glucosyl-5-O-methylvisamminol suppressed the direct interaction of histone H3 with 14-3-3ε, inhibited the aurora B kinase activity and delayed the mitotic cell cycle progression. We reports 4'-O-β-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 14-3-3ε.
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-773, Republic of Korea.
authors.forename: Jong-Su
authors.initials: JS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-773, Republic of Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-773, Republic of Korea.
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-773, Republic of Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju, Chungbuk 361-742, Republic of Korea.
authors.forename: Bu Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-773, Republic of Korea. Electronic address: keum03@dongguk.edu.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006657:Histones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D048948:14-3-3 Proteins; C000596311:4'-O-glucosyl-5-O-methylvisamminol; D002867:Chromones; D005960:Glucosides; D006657:Histones; D012694:Serine
keywords: 14-3-3ε; 4′-O-β-d-Glucosyl-5-O-methylvisamminol; Aurora B kinase; Histone phosphorylation