title: An active product of cruciferous vegetables, 3,3'-diindolylmethane, inhibits invasive properties of extravillous cytotrophoblastic cells.
abstract: OBJECTIVE
  During implantation, human trophoblastic cells have to proliferate, migrate and invade pregnant uterus. A natural product of cruciferous vegetables, 3,3'-diindolylmethane (DIM), is known to induce some stress response genes (such as glucose-regulated protein 78 kDa (GRP78)) and to have anti-invasive and pro-apoptotic effects on tumor cells. Therefore, we have investigated the potential effect of DIM on invasive extravillous cytotrophoblasts (evCTBs) cells.
  
  
  METHODS
  evCTBs were purified from first trimester trophoblasts and cultured in presence or not of DIM for 48h. In order to evaluate invasive properties of cells, they were seeded on collagen-coated insert following boyden chamber principle and matrix metalloproteinases (MMPs) and GRP78 expression was evaluated by qPCR.
  
  
  RESULTS
  We showed that DIM decreases (p=0.013) invasive properties of evCTBs. In parallel, we determined that MMP-2, -7 and -9 which are involved in evCTBs invasion and known to be regulated by DIM, are not affected by DIM in evCTBs. In contrast, MMP-1 mRNA is induced (p=0.03) and MMP-12 is decreased (p=0.01) in DIM treated cells. Moreover, DIM treatment does not affect GRP78 mRNA expression in evCTBs.
  
  
  CONCLUSIONS
  Collectively, the present results provide evidence that DIM does not impact evenly on evCTBs and cancer cells.
authors.affiliation: Laboratoire d'Hormonologie, Department of Gynaecology and Obstetrics, HUG, Maternité, Geneva, Switzerland.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaux
authors.forename: Olivier
authors.initials: O
authors.lastname: Irion
authors.forename: Marie
authors.initials: M
authors.lastname: Cohen
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007211:Indoles; D020782:Matrix Metalloproteinases; C016392:3,3'-diindolylmethane