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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 leukemiacells. 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-inducedG1 arrest was correlated with downregulation of cyclin E, with a concomitant upregulationof cyclin-dependent kinase (Cdk) inhibitors including p27, and association ofp27 with Cdk2 was markedly induced in 7,8-DHF-treated cells. We also observedthat downregulation of the phosphorylation of retinoblastoma protein (pRB) bythis flavonoid was associated with enhanced binding of pRB and the transcriptionfactor E2F-1. Overall, our results demonstrate a combined mechanism for the anticancereffects of 7,8-DHF that involves the inhibition of pRB phosphorylation and inductionof p27 as targets for 7,8-DHF.

oncology reports

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