title: Plant-derived flavones as inhibitors of aurora B kinase and their quantitative structure-activity relationships.
abstract: Although several plant-derived flavones inhibit aurora B kinase (aurB), quantitative relationships between the structural properties of plant-derived flavones and their inhibitory effects on aurB remain unclear. In this report, these quantitative structure-activity relationships were obtained. For quercetagetin, found in the Eriocaulon species, showing the best IC50 value among the flavone derivatives tested in this report, further biological tests were performed using cell-based assays, including Western blot analysis, flow cytometry, and immunofluorescence microscopy. In vitro cellular experiments demonstrated that quercetagetin inhibits aurB. The molecular-binding mode between quercetagetin and aurB was elucidated using in silico docking. Quercetagetin binds to aurB, aurA, and aurC and prevents the active phosphorylation of all three aurora kinases. In addition, quercetagetin triggers mitotic arrest and caspase-mediated apoptosis. These observations suggest that quercetagetin is an aurora kinase inhibitor. Induction of mitosis-associated tumor cell death by quercetagetin is a promising strategy for developing novel chemotherapeutic anticancer agents.
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Yearam
authors.initials: Y
authors.lastname: Jung
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Yeonjoong
authors.initials: Y
authors.lastname: Yong
authors.forename: Hyeryoung
authors.initials: H
authors.lastname: Jung
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Ahn
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000378:metabolism; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064108:Aurora Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D039262:Eriocaulaceae / Q000737:chemistry / Q000378:metabolism; D047309:Flavones / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008856:Microscopy, Fluorescence; D062105:Molecular Docking Simulation; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D002867:Chromones; D047309:Flavones; D047428:Protein Kinase Inhibitors; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064108:Aurora Kinase C; C043562:flavone; C079163:quercetagetin
keywords: aurora B kinase; flavone; flow cytometry; immunofluorescence microscopy; in silico docking; quantitative structure-activity relationship; quercetagetin