title: 7,8-dihydroxyflavone induces G1 arrest of the cell cycle in U937 human             monocytic leukemia cells via induction of the Cdk inhibitor p27 and downregulation             of pRB phosphorylation.
abstract: We investigated the mechanisms of the anti-proliferative action of 7,8-dihydroxyflavone             (7,8-DHF), a member of the flavonoid family, in U937 human monocytic leukemia             cells. We found that 7,8-DHF time-dependently inhibited the growth of U937 cells,             arresting them in the G1 phase of their cell cycle and inducing apoptosis. 7,8-DHF-induced             G1 arrest was correlated with downregulation of cyclin E, with a concomitant upregulation             of cyclin-dependent kinase (Cdk) inhibitors including p27, and association of             p27 with Cdk2 was markedly induced in 7,8-DHF-treated cells. We also observed             that downregulation of the phosphorylation of retinoblastoma protein (pRB) by             this flavonoid was associated with enhanced binding of pRB and the transcription             factor E2F-1. Overall, our results demonstrate a combined mechanism for the anticancer             effects of 7,8-DHF that involves the inhibition of pRB phosphorylation and induction             of p27 as targets for 7,8-DHF.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental                     Medicine, Busan 614-714, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Chan Gil
authors.initials: CG
authors.lastname: Kim
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D050687:E2F1 Transcription Factor / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: C485383:6,7-dihydroxyflavone; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; D047309:Flavones; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27