scutellarein 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

The ubiquitin-proteasome pathway plays an important role in regulating apoptosis and the cell cycle. Recently, proteasome inhibitors have been shown to have antitumor effects and have been used in anticancer therapy for several cancers such as multiple myeloma. Although some flavones, such as apigenin, chrysin and luteolin, have a specific role in the inhibition of proteasome activity and induced apoptosis in some reports, these findings did not address all flavone types. To further investigate the proteasome-inhibitory mechanism of flavonoids, we examined the inhibitory activity of 5,6,7-trihydroxyflavone, baicalein and 5,6,7,4'-tetrahydroxyflavone, scutellarein on extracted proteasomes from mice and cancer cells. Unlike the other flavones, baicalein and scutellarein did not inhibit proteasome activity or accumulate levels of ubiquitinated proteins. These results indicate that flavones with hydroxy groups at positions 5, 6 and 7 of the A-ring lack the anti-proteasome function.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apigenin; Apoptosis; Flavanones; Flavones; HCT116 Cells; Humans; Jurkat Cells; Molecular Structure; Neoplasms; Phytotherapy; Plant Extracts; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Rabbits; Structure-Activity Relationship

Exploration for inhibitors against expression of IgE receptor (Fc epsilonRI) on human mast cell, a significant trigger to acute and chronic allergic symptoms, disclosed epigallocatechin gallate (EGCG), epicatechin gallate, and gallocatechin gallate as active principles. Additionally, the anthocyanidin, delphinidin, and the flavone, tricetinidin, possessing a pyrogallol function were also revealed to suppress expression of Fc epsilonRI. Structure-activity relationship analysis among catechins, anthocyanidins, and flavones revealed the pyrogallol moiety to be crucial for biological potency. Furthermore, EGCG was clarified to reduce generation of gamma-chain subunit to suppress expression of Fc epsilonRI on human mast cells.

Topics: Anthocyanins; Anti-Allergic Agents; Catechin; Cell Line; Flavones; Flavonoids; Gene Expression; Humans; Hypersensitivity; Mast Cells; Receptors, IgE