Laboratory of Cell Cycle and Cancer, College of Life Sciences, Capital Normal University, HaiDian District, Beijing 100048, China.
Mol Cell Biochem. 2011 Dec;358(1-2):345-54. doi: 10.1007/s11010-011-0985-0. Epub 2011 Jul 15.
3,3'-Diindolylmethane (DIM) is a potential cancer preventive phytochemical derived from Brassica vegetables. The effects of DIM on cell-cycle regulation in both estrogen-dependent MCF-7 and estrogen receptor negative p53 mutant MDA-MB-468 human breast cancer cells were assessed in this study. DIM inhibited the breast cancer cell growth in vitro and in vivo, and caused cell-cycle arrest by down-regulating protein levels of cell-cycle related kinases CDK1, CDK2, CDK4, and CDK6, as well as Cyclin B1 and Cdc25A. Meanwhile, it was revealed that Ser(124) phosphorylation of Cdc25A is primarily responsible for the DIM-induced Cdc25A degradation. Furthermore, treatment of MCF-7 cells with DIM increased miR-21 expression and down-regulated Cdc25A, resulting in an inhibition of breast cancer cell proliferation. These observations collectively suggest that by differentially modulating cellular signaling pathways DIM is able to arrest the cell-cycle progression of human breast cancer cells.
3,3'-二吲哚甲烷（DIM）是一种源自十字花科蔬菜的有潜力的防癌植物化学物质。本研究评估了 DIM 对雌激素依赖性 MCF-7 和雌激素受体阴性 p53 突变 MDA-MB-468 人乳腺癌细胞中细胞周期调控的影响。DIM 在体外和体内抑制乳腺癌细胞生长，并通过下调细胞周期相关激酶 CDK1、CDK2、CDK4 和 CDK6 以及细胞周期蛋白 B1 和 Cdc25A 的蛋白水平导致细胞周期停滞。同时，研究表明 Cdc25A 的 Ser(124)磷酸化主要负责 DIM 诱导的 Cdc25A 降解。此外，DIM 处理 MCF-7 细胞可增加 miR-21 的表达并下调 Cdc25A，从而抑制乳腺癌细胞增殖。这些观察结果共同表明，通过差异化调节细胞信号通路，DIM 能够阻止人乳腺癌细胞的细胞周期进程。
