6-7-dihydroxyflavone and Leukemia--Myeloid

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.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Down-Regulation; E2F1 Transcription Factor; Flavones; G1 Phase Cell Cycle Checkpoints; Humans; Leukemia, Myeloid; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Retinoblastoma Protein; Transcriptional Activation