Studies on anti-metastatic and anti-invasive effects of harmine using highly metastatic murine B16F-10 melanoma cells.
Harmine is a beta-carboline alkaloid from the plant Peganum harmala. We evaluated the anti-metastatic activity of harmine using in vivo mouse lung metastasis and in vitro models. Lung metastasis was induced using B16F-10 melanoma cells in C57BL6 mice by three different modalities of administration simultaneous, prophylactic, and after tumor development. Harmine significantly inhibited tumor nodule formation in the lung tissue and decreased various biochemical parameters associated with lung metastasis. Higher expression levels of pro-metastatic genes such as matrix metalloproteinase-9 (MMP-9), extracellular signalenregulated kinase (ERK), and vascular endothelial factors (VEGFs), all of which play important roles in cancer cell migration and invasion, were observed in the metastatic group compared with normal, but were all down-regulated by treatment with harmine. Harmine was also able to inhibit tumor cell proliferation, invasion, and migration in vitro. In conclusion, harmine exerts anti-metastatic activity and this effect could be linked to the metastasis-related signaling pathway that includes ERK, VEGF, and MMPs.