Inhibition of experimental metastasis by enzyme inhibitors from microorganisms and plants

Various antibacterial compounds, antitumor compounds, enzyme inhibitors and recent signal transduction inhibitors have been discovered from microorganisms and plants. Therefore, it should be possible to find antimetastatic compounds from these sources, if a simple assay system is available. We isolated several enzyme inhibitors from nature to inhibit experimental metastasis. Leupeptin is an old protease inhibitor and inhibited blood-borne lung metastasis of hepatoma cells in rats. A leupeptin analogue inhibiting urokinase inhibited in vitro invasion of human fibrosarcoma cells. Alpha-glucosidase inhibitors such as epi-CPL and baicalein inhibited in vitro invasion and in vivo metastasis of mouse melanoma cells. A mannosidase inhibitor, mannostatin A, also inhibited in vitro invasion of mouse melanoma cells. Oncogene function inhibitors induce normal phenotypes in the oncogene-expressing cells. As expected, they inhibited tumor cell invasion in vitro.