3,3′-Diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways

Metastasis of cancer is a multifactorial disease and is the main cause of death in patients with malignancy. This disease demands treatments which may target multiple dys-regulated cellular pathways in cancer cells. The anti-tumor and anti-metastatic properties of natural products in cancer prevention have been confirmed by several epidemiological studies, with cruciferous vegetables being especially protective against many cancers. In this study, we evaluated the anti-carcinogenic effects of 3,3'-diindolylmethane (DIM), which is a bioactive compound present in cruciferous vegetables and a widely used dietary supplement, on events commonly observed during metastasis using in vitro adhesion, migration and invasion assays. Our results indicate that DIM inhibits human cancer cell in vitro proliferation, adhesion, migration and invasion. Western blot analyses show that this inhibition of cell proliferation by DIM is exerted by combined suppression of AKT and ERK pathways. Furthermore, DIM also leads to down-regulation of G1-S cell cycle markers: cyclin D1, cdk6 and cdk4. These findings may lead to development of a novel preventive and/or therapeutic dietary supplement for patients diagnosed with cancer or predisposed to developing certain cancers.