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
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- Published online on: April 23, 2012 https://doi.org/10.3892/or.2012.1773
- Pages: 353-357
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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.
