Anticarcinogenic Effect and Enhancement of Metastatic Potential of BALB/c 3T3 Cells by Ginsenoside Rh2

Abstract

It has been reported that ginsenoside Rh₂, a purified ginseng saponin with a dammarane skeleton, has anticarcinogenic effects on mammalian cells. To determine the significance of these effects on multistage carcinogenesis, we utilized the BALB/c 3T3 cell system. In an in vitro two–stage neoplas–tic transformation assay, the initiating activity of 3–methylcholanthrene (3–MCA) was suppressed by Rh₂ (>lxlO^–5M) in both BALB/c 3T3 A31–1–1 cells and the more carcinogen–susceptible variant A31–1–13 cells. The suppressive effects in this concentration range were thought to be caused by suppression of DNA replication via indirect Cdk2 inhibition. On the other hand, the promotion steps of both the target cells were not affected by Rh₂ even if the transformation frequency was enhanced by a tumor promoter, 12–O–tetradecanoylphorbol–13–acetate (TPA). To examine the other effects of Rh₂ on carcinogenesis, we turned our attention to the metastatic phenotype. Using metastatic src–transformed A31–1–1 cells, we found that Rh₂ augmented the metastatic potential in an experimental metastasis assay. These data indicate that Rh₂ has diverse effects on the expression of the transformed phenotype in BALB/c 3T3 cells, but support the idea that growth suppression is likely to be a major mechanism of the anticarcinogenic effects of Rh₂.