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KMID : 0603520030080020114
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Journal of Korean Association of Cancer Prevention
2003 Volume.8 No. 2 p.114 ~ p.123
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Inhibitory Effect of Ginsenoside Rb1 on Activities of Oncogenic ras
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Yi Sun-Ju
Jhun Byung-Hak
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Abstract
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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.
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KEYWORD
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Ginsenoside, Oncogenic ras, Microinjection, DNA synthesis, c-Jun
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