Anticarcinogenic effect and enhancement of metastatic potential of BALB/c 3T3 cells by ginsenoside Rh-2

It has been reported that ginsenoside Rh-2, a purified ginseng saponin with a dammarane skeleton, has anticarcinogenic effects on mammalian cells. To determine the significance of these effects on multistage carcinogenesis, w e utilized the BALB/c 3T3 cell system. In an in vitro two-stage neoplastic transformation assay, the initiating activity of 3-methylcholanthrene (3-MC A) was suppressed by Rh-2 (greater than or equal to 1x10(-5) M) in both BAL B/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 af fected by Rh-2 even if the transformation frequency was enhanced by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). To examine the other effects of Rh-2 on carcinogenesis, we turned our attention to the metastat ic phenotype. Using metastatic src-transformed A31-1-1 cells, we found that Rh-2 augmented the metastatic potential in an experimental metastasis assa y. These data indicate that Rh, has diverse effects on the expression of th e transformed phenotype in BALB/c 3T3 cells, but support the idea that grow th suppression is likely to be a major mechanism of the anticarcinogenic ef fects of Rh-2.