title: 3,3'-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation.
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 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.
authors.affiliation: Laboratory of Cell Cycle and Cancer, College of Life Sciences, Capital Normal University, HaiDian District, Beijing 100048, China. lantianmeiyu1985@gmail.com
authors.forename: Yucui
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D059748:Proteolysis / Q000187:drug effects*; D012694:Serine / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D020687:cdc25 Phosphatases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D007211:Indoles; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012694:Serine; D020687:cdc25 Phosphatases; C016392:3,3'-diindolylmethane