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, we utilized the BALB / c 3T3 cell system. In an in vitro two-stage neoplastic transformation assay, the initiating activity of 3-methylcholanthrene (3-MCA) was suppressed by Rh(2) (>or= 1 x 10(-5) M) 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 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 metastatic phenotype. Using metastatic src-transformed A31-1-1 cells, we found that Rh(2) augmented the metastatic potential in an experimental metastasis assay. These data indicate that Rh(2) 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 Rh(2).
Tatsuka
M
M
Department of Regulatory Radiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8553. haruo@hiroshima-u.ac.jp
Maeda
M
M
Ota
T
T
D016475:3T3 Cells; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D042846:CDC2-CDC28 Kinases; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D036145:Ginsenosides; D012503:Saponins; D008748:Methylcholanthrene; C055305:ginsenoside Rh2; D015688:Oncogene Protein pp60(v-src); D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases