title: Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex.
abstract: Myricetin, a naturally occurring flavonol, has been shown to inhibit the proliferation of human hepatoma HepG2 cells and to induce G2/M phase arrest. However, the underlying mechanisms of Myricetin activity have yet to be revealed. The aim of the present study was to clarify the molecular mechanisms of cell cycle arrest induced by myricetin in HepG2 cells. The MTT assay confirmed that exposure of HepG2 cells to myricetin triggered G2/M phase arrest. Western blot analysis showed that myricetin increased the protein levels of the p53/p21 cascade, and markedly decreased Cdc2 and cyclin B1 protein levels in HepG2 cells. Additionally, myricetin treatment resulted in the up-regulation of Thr14/Tyr15 phosphorylated (inactive) Cdc2 and p27, and the down-regulation of CDK7 kinase protein, as well as CDK7-mediated Thr161 phosphorylated (active) Cdc2. These data indicate that a decrease in cyclin B/Cdc2 complex activity mediated G2/M phase arrest induced by myricetin in HepG2 cells. This novel finding provides insight into the potential applications of myricetin in the treatment of hepatocellular carcinoma.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Zhejiang 310029, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Zu-Quan
authors.initials: ZQ
authors.lastname: Zou
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Xu
authors.forename: Ying-Zhuo
authors.initials: YZ
authors.lastname: Shen
authors.forename: Duo
authors.initials: D
authors.lastname: Li
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D019926:Cyclin B; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; C040015:myricetin; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human