Inhibition of in vitro Tumor Cell Invasion by Ginsenoside Rg₃

Abstract

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, Rb2, 20(R)‐ginsenoside Rg2 and 20(S)‐ginsenoside Rg3 (a stereoisomer of Rg3), showed little inhibitory activity. Neither Rh1, Rh2, 20(R)‐ginsenosides Rh1 Rb1, Rc nor Re had any effect. The effective ginsenoside, Rg3, 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 Rg3 on molecular events associated with the invasion induced by LPA was analyzed in order to understand the mechanism of the inhibition. Rg3, which suppressed the invasion induced by LPA, dose‐dependently inhibited the LPA‐triggered rise of intracellular Ca2+. Protein tyrosine phosphorylation triggered by LPA was not inhibited by Rg3.

20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway

“…This in turn results in the activation of downstream caspase-3, which cleaves ParP (24,25). recent data indicate that the mitochondrial pathway is controlled and regulated by Bcl-2 family protein (5,(22)(23)(24)(25). Bcl-2 family proteins such as Bcl-2 and Bax have been identified as major regulators in controlling the release of mitochondrial cytochrome c (26).…”

Induction by bombesin of peritoneal metastasis of gastric cancers induced by N -methyl- N ?-nitro- N -nitrosoguanidine in Wistar rats

“…Imamura et al [21] found that the addition of serum to a suspension of highly invasive tumor cells induced an increase in the intracellular pH, as well as a transient elevation of intracellular calcium, whereas the addition of serum to a poorly invasive clone did not result in changes in intracellular pH or calcium. Moreover, we [22] found that the addition of 1-oleoyllysophosphatidic acid to rat ascites hepatoma cells resulted in an instantaneous increase in intracellular calcium, but when these cells were pretreated with the antimetastatic agent, ginsenoside Rg3, the intracellular calcium spike induced by 1-oleoyl-lysophosphatidic acid was completely abolished. Hellmich et al [23] found that bombesin induced either intracellular calcium oscillations or biphasic elevation in intracellular calcium, and that the activation of mitogen-activated protein kinase (MAPK) kinase (MEK) was important for maintaining the elevated intracellular calcium levels induced by bombesin.…”

Ginsenoside Rg3 enhances the inhibitory effects of chemotherapy on esophageal squamous cell carcinoma in mice

“…Ginsenoside Rg3, the active ingredient extracted from Panax ginseng, possesses anticancer properties and exerts various pharmacological effects (6,7). Previous studies demonstrated that ginsenoside Rg3 may inhibit cancer growth in vitro and in vivo and is considered to be relatively safe (8)(9)(10).…”