Kimchi and an active component, beta-sitosterol, reduce oncogenic H-Ras(v12)-induced DNA synthesis

The Korean fermented vegetable food, kimchi, has been demonstrated to have anticancer functional properties. This study examined the effect of kimchi samples, methanol extracts of commercially grown baechu cabbage kimchi (CK) and organically grown baechu cabbage kimchi (OK), as well as the dichloromethane fraction (DCM fr.) from CK, and the active compound (AC), which has been identified as largely beta-sitosterol, from DCM fr., on the Ras-dependent signaling pathway. CK, OK, and DCM fr. exhibited a greater inhibition against the proliferation of Rat2 fibroblasts transformed with Ras(v12) (HO6) than parental Rat2 fibroblasts. In addition, OK and DCM fr. showed a higher inhibitory effect than CK. Furthermore, we employed the single-cell microinjection technique, combined with 3-bromo-5'-deoxyuridine incorporation, to examine the effects of kimchi samples on DNA synthesis induced by microinjected oncogenic Ras(v12). When the DCM fr. and AC were used to treat Rat1 fibroblasts overexpressing human insulin receptors (HIRc-B) and microinjected with oncogenic H-Ras(v12), the DNA synthesis of injected cells was decreased, suggesting that kimchi might block the signaling pathway of oncogenic Ras(v12), thus preventing the proliferation of transformed cells. This study provides additional evidence that kimchi and its active components, including beta-sitosterol, have potential in both the prevention and treatment of cancer, and presents convincing evidence that the anticancer effects may be a result of an inhibition of Ras oncogene signaling.