title: FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells.
abstract: Although 3,3'-diindolylmethane (DIM) has been suggested to reduce the risk of colorectal cancer, the underlying biological mechanism is not clearly understood. In the present study, we investigated the effect of DIM on the migratory and invasive activities of the human colorectal cancer cell lines DLD-1 and HCT116. DIM significantly inhibited the migration and invasion of colorectal cancer cells as assessed by wound healing and Matrigel invasion assays. The migratory ability of the DLD-1 and HCT116 cells was significantly reduced by DIM at 24 and 48 h. DIM also significantly inhibited the invasion rate of the DLD-1 and HCT116 cells in a dose-dependent manner. The mRNA expression levels of urokinase type plasminogen activator (uPA) and matrix metalloprotease 9 (MMP9) were significantly attenuated, whereas expression of E-cadherin mRNA was significantly enhanced, following DIM treatment. DIM also decreased the protein levels of uPA and MMP9, yet significantly increased E-cadherin protein expression. In addition, DIM significantly reduced the mRNA and protein levels of FOXM1 in the DLD-1 and HCT116 cells. Our results suggest that DIM can influence the cell migratory and invasive properties of human colorectal cancer cells and may decrease the invasive capacity of colorectal cancer through downregulation of uPA and MMP9 mediated by suppression of the transcription factor FOXM1.
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Catholic University of Pusan, Busan, Republic of Korea.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015820:Cadherins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D007211:Indoles; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C016392:3,3'-diindolylmethane