Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 332, Issue 1-2, Pages 33-41Publisher
SPRINGER
DOI: 10.1007/s11010-009-0171-9
Keywords
Myricetin; Akt; Modeling; Cell transformation
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Funding
- Frontier Science Research Center of Kagoshima University
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Akt, a serine/threonine kinase, is a critical regulator in many cellular processes including cell growth, proliferation, and apoptosis. In this study, we found that myricetin, a typical flavonol existing in many fruits and vegetables, could directly target Akt to inhibit cell transformation. Binding assay revealed that myricetin bound to Akt directly by competing with ATP. In vitro and ex vivo data confirmed that myricetin inhibited the phosphorylation and kinase activity of Akt. Molecular modeling suggested that myricetin easily docks to the ATP-binding site of Akt with hydrogen bonds. Signaling analysis data further demonstrated that myricetin inhibited Akt-mediated activator protein-1 (AP-1) transactivation, cyclin D1 expression and cell transformation. Overall, our results indicate that Akt is a direct target for myricetin to inhibit cell transformation.
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