Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: Involvement of CDK4 and p2l

Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: Involvement of CDK4 and p2l
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DOI:
10.1080/01635580701419030
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发表时间:
2007-01-01
影响因子:
2.9
通讯作者:
Choi, Eun Jeong
Choi, Eun Jeong
中科院分区:
医学4区
文献类型:
--
作者:
Choi, Eun Jeong

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本研究旨在探讨橙皮苷对乳腺癌MCF-7细胞增殖和细胞周期阻滞的影响,并探讨其作用机制。Hesperetin以剂量依赖的方式显著抑制细胞增殖,在48和72小时后,导致细胞周期阻滞在G1期。在g1期相关蛋白中,hesperetin在处理48 h和72 h的细胞中下调细胞周期蛋白依赖性激酶(CDKs)和细胞周期蛋白,上调p21Cip1和p27(Kip1)。处理72 h后,这些现象更为明显。高浓度Hesperetin处理72 h后,CDK2、CDK4和cyclin d均降低,Hesperetin增加了CDK4与p21Cip1的结合,但不增加p27(Kip1)和p57(Kip2)的结合。综上所述,我们的数据首次表明CDK4和p21(Cip2)的调控可能参与了MCF-7细胞hesperetin的抗癌活性途径。
This study was to investigate the effects of hesperetin on cell proliferation and cell cycle arrest and explored the mechanism for these effects in breast carcinoma MCF-7 cells. Hesperetin significantly inhibited cell proliferation in a dose-dependent manner a er treatment for 48 and tft 72 h and resulted in significant cell cycle arrest in the G1 phase. In the G1-phase related proteins, hesperetin downregulates the cyclin-dependent kinases (CDKs) and cyclins and upregulates p21Cip1 and p27(Kip1) in cells treated with hesperetin for 48 h and 72 h. After 72 h treatment, these phenomenons were more pronounced. Hesperetin treatment at high concentration for 72 h resulted in a decrease in CDK2 and CDK4 together with cyclin D. In addition, hesperetin increases the binding of CDK4 with p21Cip1 but not p27(Kip1) or p57(Kip2). Taken together, our data suggest for the first time that the regulation of CDK4 and p21(Cip2) may participate in the anticancer activity pathway of hesperetin in MCF-7 cells.