Akt is a direct target for myricetin to inhibit cell transformation.
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.
Kumamoto
Takuma
T
United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto 1-21-24, Kagoshima City, 890-0065, Japan.
Fujii
Makoto
M
Hou
De-Xing
DX
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D016195:G2 Phase; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D005419:Flavonoids; D018808:Transcription Factor AP-1; D019938:Cyclin D1; C040015:myricetin; D000255:Adenosine Triphosphate; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010959:Tissue Plasminogen Activator