title: Quercetin inhibits a large panel of kinases implicated in cancer cell biology.
abstract: Flavonoids are polyphenolic secondary metabolites from plants that possess a common phenylbenzopyrone structure (C6-C3-C6). Depending upon variations in their heterocyclic C-ring, flavonoids are categorised into one of the following groups: flavones, flavonols, flavanones, flavanols, anthocyanidins, isoflavones or chalcones. Flavonols include, among others, the molecules quercetin, myricetin and kaempferol. The anticancer activity of flavonols was first attributed to their electron-donating ability, which comes from the presence of phenolic hydroxyl groups. However, an emerging view is that flavonoids, including quercetin, may also exert modulatory actions in cells by acting through the protein kinase and lipid kinase signalling pathways. Data from the current study showed that 2 μM quercetin, a low concentration that represents less than 10% of its IC50 growth-inhibitory concentration as calculated from the average of eight distinct cancer cell lines, decreased the activity of 16 kinases by more than 80%, including ABL1, Aurora-A, -B, -C, CLK1, FLT3, JAK3, MET, NEK4, NEK9, PAK3, PIM1, RET, FGF-R2, PDGF-Rα and -Rß. Many of these kinases are involved in the control of mitotic processes. Quantitative video microscopy analyses revealed that quercetin displayed strong anti-mitotic activity, leading to cell death. In conclusion, quercetin partly exerts its anticancer activity through the inhibition of the activity of a large set of kinases. Quercetin could be an interesting chemical scaffold from which to generate novel derivatives possessing various types of anti-kinase activities.
authors.affiliation: Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Rainatou
authors.initials: R
authors.lastname: Boly
authors.forename: Thierry
authors.initials: T
authors.lastname: Gras
authors.forename: Touria
authors.initials: T
authors.lastname: Lamkami
authors.forename: Pierre
authors.initials: P
authors.lastname: Guissou
authors.forename: Didier
authors.initials: D
authors.lastname: Serteyn
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Jacques
authors.initials: J
authors.lastname: Dubois
mesh_terms: D000818:Animals; D003585:Cell Biology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D028183:Loranthaceae / Q000737:chemistry; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D018411:Spodoptera
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011794:Quercetin; D010770:Phosphotransferases