OBJECTIVES: 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.
MATERIALS AND 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.