[en] 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-R· 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 antikinase activities.
Research Center/Unit :
CORD - Centre de l'Oxygène, Recherche et Développement - ULiège
Boly, Rainatou; Université Libre de Bruxelles - ULB > Faculté de Pharmacie > Laboratoire de Chimie Bioanalytique
Gras, Thierry; Université Libre de Bruxelles - ULB > Faculté de Pharmacie > Laboratoire de Toxicologie
Lamkami, Touria; Université Libre de Bruxelles - ULB > Faculté de Pharmacie > Laboratoire de Chimie BioAnalytique, Toxicologie et Chimie Physique Appliquée
Guissou, Pierre; Université de Ouagadougou, Ouagadougou, Burkina Faso > UFR/Sciences de la Santé > Laboratoire de Pharmacologie-Toxicologie Appliquée, UFR/Sciences de la Santé,
Serteyn, Didier ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Kiss, Robert; Université Libre de Bruxelles - ULB > Faculté de Pharmacie > Laboratoire de Toxicologie
Dubois, Jacques; Université Libre de Bruxelles - ULB > Faculté de Pharmacie > Laboratoire de Chimie BioAnalytique, Toxicologie et Chimie Physique Appliquée
Language :
English
Title :
Quercetin inhibits a large panel of kinases implicated in cancer cell biology.
Publication date :
2011
Journal title :
International Journal of Oncology
ISSN :
1019-6439
eISSN :
1791-2423
Publisher :
DA Spandidos, Athens, Greece
Volume :
38
Pages :
833-842
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
The current study has been carried out thanks to grants awarded by Wallonnie- Bruxelles International (WBI).
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