morin and flavone

Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising targets for drug development. In most cases, the catalytic domain is targeted; however, it is also possible to target membrane associations in order to regulate protein activity. In this study, we established a novel method to study protein-lipid interactions and screened for flavonoid-derived antagonists of PtdIns(3,4,5)P

Topics: 3-Phosphoinositide-Dependent Protein Kinases; Binding Sites; Flavones; Flavonoids; Flavonols; Liposomes; Molecular Docking Simulation; Phosphatidylinositol Phosphates; Pleckstrin Homology Domains; Protein Binding; Quantitative Structure-Activity Relationship

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.

Topics: Apoptosis; Aurora Kinase A; Aurora Kinase B; Aurora Kinase C; Binding Sites; Chromones; Eriocaulaceae; Flavones; G2 Phase Cell Cycle Checkpoints; HCT116 Cells; Humans; M Phase Cell Cycle Checkpoints; Microscopy, Fluorescence; Molecular Docking Simulation; Phosphorylation; Protein Kinase Inhibitors; Protein Structure, Tertiary; Quantitative Structure-Activity Relationship

Mast cells are involved in allergic and inflammatory reactions. These cells are also increased in the bone marrow, skin, and other organs in systemic mastocytosis. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory activities. Some flavonoids, like quercetin, inhibit the growth of certain malignant cells in culture. Quercetin also inhibits histamine release and induces accumulation of secretory granules in rat basophilic leukemia cells.. We investigated the effect of five flavonoids: flavone, kaempferol, morin, myricetin, and quercetin at 1, 10, and 100 microM on proliferation and secretory mediator content (beta-hexosaminidase, histamine, and tryptase) in human leukemic mast cells (HMC-1), the doubling time of which was about 2 d.. Flavone and kaempferol at 100 microM inhibited cell proliferation over 80% on either day 3, 4, or 5 of culture. Quercetin showed this level of inhibition only on day 5, myricetin inhibited by 50% at days 3-5, whereas morin's inhibition was < 20%. All flavonoids (except morin) at 100 microm increased histamine and tryptase content, but not beta-hexosaminidase, equally at days 3 and 4 of culture quercetin also increased the development of secretory granules.. These results indicate that certain flavonoids can inhibit HMC-1 proliferation, induce secretory granule development and the accumulation of mediators.

Topics: beta-N-Acetylhexosaminidases; Cell Division; Cell Survival; Flavones; Flavonoids; Histamine; Humans; Kaempferols; Leukemia, Mast-Cell; Mast Cells; Microscopy, Electron; Quercetin; Secretory Vesicles; Serine Endopeptidases; Tryptases; Tumor Cells, Cultured