Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714, Republic of Korea.
Oncol Rep. 2012 Jul;28(1):353-7. doi: 10.3892/or.2012.1773. Epub 2012 Apr 23.
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.
我们研究了黄酮类家族成员 7,8-二羟基黄酮（7,8-DHF）在 U937 人单核白血病细胞中的抗增殖作用机制。我们发现 7,8-DHF 可时间依赖性地抑制 U937 细胞的生长，将其阻滞在细胞周期的 G1 期并诱导细胞凋亡。7,8-DHF 诱导的 G1 期阻滞与细胞周期蛋白 E 的下调相关，同时细胞周期蛋白依赖性激酶（Cdk）抑制剂包括 p27 的表达上调，并且在 7,8-DHF 处理的细胞中 p27 与 Cdk2 的结合明显增加。我们还观察到，这种黄酮类化合物下调视网膜母细胞瘤蛋白（pRB）的磷酸化与 pRB 和转录因子 E2F-1 的结合增强相关。总的来说，我们的结果表明，7,8-DHF 的抗癌作用涉及抑制 pRB 磷酸化和诱导 p27 作为 7,8-DHF 的作用靶点的综合机制。
