Capital Normal University, Beijing, China.
Anticancer Drugs. 2010 Oct;21(9):814-22. doi: 10.1097/CAD.0b013e32833e53ea.
3,3'-Diindolylmethane (DIM) is a potential chemopreventive phytochemical derived from Brassica vegetables. In this study, we assessed 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. In-vitro culture studies showed that DIM dose dependently inhibited the proliferation of both cells. In addition, in-vivo xenograft model showed that DIM strongly inhibited the development of human breast tumors. Fluorescence activated cell sorter analysis showed a DIM-mediated G2/M cell cycle arrest in MCF-7 and MDA-MB-468 cells. Western blot analysis showed that DIM downregulated the expression of cyclin-dependent kinases 2 and 4 and Cdc25A, which plays an important role in G2/M phase. Furthermore, treatment of MCF-7 cells with DIM, which increased microRNA 21 expression, caused a downregulation of Cdc25A, resulting in an inhibition of breast cancer cell proliferation. Taken together, our data show that DIM is able to stop the cell cycle progression of human breast cancer cells regardless of their estrogen-dependence and p53 status, by differentially modulating cell cycle regulatory pathways. The modulation of microRNA 21 mediates the DIM cell cycle regulator effect in MCF-7 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化学预防植物化学物质。在这项研究中，我们评估了 DIM 对依赖雌激素的 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。体外培养研究表明，DIM 呈剂量依赖性地抑制这两种细胞的增殖。此外，体内异种移植模型表明，DIM 强烈抑制人乳腺癌肿瘤的发展。荧光激活细胞分选分析显示 DIM 介导 MCF-7 和 MDA-MB-468 细胞的 G2/M 细胞周期阻滞。Western blot 分析表明，DIM 下调细胞周期蛋白依赖性激酶 2 和 4 以及 Cdc25A 的表达，Cdc25A 在 G2/M 期发挥重要作用。此外，用 DIM 处理 MCF-7 细胞，增加 microRNA 21 的表达，导致 Cdc25A 的下调，从而抑制乳腺癌细胞的增殖。总之，我们的数据表明，DIM 能够阻止人乳腺癌细胞的细胞周期进程，而不论其雌激素依赖性和 p53 状态如何，通过差异调节细胞周期调控途径。microRNA 21 的调节介导了 DIM 在 MCF-7 细胞中的细胞周期调节剂作用。
