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Akt is a direct target for myricetin to inhibit cell transformation

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Abstract

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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Acknowledgments

This study was partly supported by the fund of Frontier Science Research Center of Kagoshima University granted to D.-X. Hou.

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Authors and Affiliations

  1. United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto 1-21-24, Kagoshima City, 890-0065, Japan

    Takuma Kumamoto, Makoto Fujii & De-Xing Hou

  2. Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima City, 890-0065, Japan

    Makoto Fujii & De-Xing Hou

Authors
  1. Takuma Kumamoto
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  2. Makoto Fujii
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  3. De-Xing Hou
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Correspondence to De-Xing Hou.

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Kumamoto, T., Fujii, M. & Hou, DX. Akt is a direct target for myricetin to inhibit cell transformation. Mol Cell Biochem 332, 33–41 (2009). https://doi.org/10.1007/s11010-009-0171-9

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  • DOI: https://doi.org/10.1007/s11010-009-0171-9

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