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3,3′-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation

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Abstract

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 Ser124 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.

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Acknowledgments

The author wishes to thank Carolyn Paisie (Ohio State University) for comments on this manuscript. This research was supported by 211 Special fund (105609101) from Ministry of Education of the People’s Republic of China.

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  1. Laboratory of Cell Cycle and Cancer, College of Life Sciences, Capital Normal University, 105 Xi San Huan Road, HaiDian District, Beijing, 100048, China

    Yucui Jin

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Correspondence to Yucui Jin.

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Jin, Y. 3,3′-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation. Mol Cell Biochem 358, 345–354 (2011). https://doi.org/10.1007/s11010-011-0985-0

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