Inhibition of in vitro Tumor Cell Invasion by Ginsenoside Rg(3)

The effect of plant glycosides on tumor cell invasion was examined. Among the glycosides tested, ginsenoside Rgs was found to be a potent inhibitor of invasion by rat ascites hepatoma cells (MM1), B16FE7 melanoma cells, human small cell lung carcinoma (OC10), and human pancreatic adenocarcinoma (PSN‐1) cells, when examined in a cell monolayer invasion model. Structurally analogous ginsenosides, Rb(2), 20(R)‐ginsenoside Rg(2) and 20(S)‐ginsenoside Rg(3) (a stereoisomer of Rg(3)), showed little inhibitory activity. Neither Rh(1), Rh(2), 20(R)‐ginsenosides Rh(1) Rb(1), Rc nor Re had any effect. The effective ginsenoside, Rg(3), tended to inhibit experimental pulmonary metastasis by highly metastatic mouse melanoma B16FE7 cells as well. Taking account of our previous finding that 1‐oleoyl‐lysophosphatidic acid (LPA) induced invasion by MM1 cells in the monolayer invasion model, the effect of Rg(3) on molecular events associated with the invasion induced by LPA was analyzed in order to understand the mechanism of the inhibition. Rg(3), which suppressed the invasion induced by LPA, dose‐dependently inhibited the LPA‐triggered rise of intracellular Ca(2+). Protein tyrosine phosphorylation triggered by LPA was not inhibited by Rg(3).