The ras genes, which have three isoforms, H-ras, K-ras and N-ras, were mutated up to 30% of human tumors. It is well known that components of ginseng have anticancer actions, but it is not reported that components of ginseng have any effect on ras-mediated cancer. In this study, we have examined the inhibitory effect of ginsenoside Rb1 and Rg1 on oncogenic ras-mediated oncogenicity. Oncogenic H-rasV12, K-rasV12 and N-rasN12 were prepared as GST fusion proteins and microinjected into quiescent Rat 1 fibroblasts. The injected oncogenic ras proteins induced DNA synthesis and c-Jun protein expression. Pretreatment of Rb1 suppressed H-rasV12- and N-rasN12-induced DNA synthesis, but not c-Jun expression. In contrast, Rg1 had no effect. SRE promoter was activated by transient transfection of oncogenic H-, K- and N-ras. Pretreatment of Rb1 suppressed oncogenic N-rasN12-induced SRE activation but not oncogenic H-rasV12 and K-rasV12. Next, the effect of Rb1 and Rg1 on the proliferation of oncogenic H-, K- and N-ras-transformed Rat 2 fibroblasts was examined. The proliferation of the ras-transformed cells was not affected by Rb1 and Rg1. The post-translational modification of ras is necessary for the activation. The pretreatment of Rb1 and Rg1 on oncogenic ras-transformed cellsg did not inhibit the modification of ras. From these results, we found that Rb₁ has an inhibitory effect on oncogneic ras mitogenic signaling. Particularly isoform specific pattern was observed.

Keywords: Gisenoside, Oncogenic ras, Microinjection, DNA synthesis, c-Jun