Anti-metastatic activity of Acanthopanax senticosus extract and its possible immunological mechanism of action.

Antitumor and immunomodulatory activities of an aqueous extract (GF100) of Acanthopanax senticosus were examined. In experimental lung metastasis of colon26-M3.1 carcinoma cells, intravenous (i.v.) administration of GF100 2 days before tumor inoculation significantly inhibited lung metastasis in a dose-dependent manner. The i.v. administration of GF100 also exhibited the therapeutic effect on tumor metastasis of colon26-M3.1 cells, when it was injected 1 day after tumor inoculation. In an in vitro cytotoxicity analysis, GF100 at the concentration up to 1000 microg/ml did not affect the growth of colon26-M3.1 cells. In contrast, GF100 enhanced the responsiveness to a mitogen, concanavalin A (ConA), of splenocytes in a dose-dependent manner. Peritoneal macrophage stimulated with GF100 produced various cytokines such as IL-1beta, TNF-alpha, IL-12 and IFN-gamma in an in vitro experiment. The macrophages obtained from the mice which were injected with GF100 (500 microg) 3 days before the assay showed significantly higher tumoricidal activity against tumor cells than that of the untreated macrophages. In addition, the i.v. administration of GF100 significantly augmented NK cytotoxicity to Yac-1 cells. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of GF100 on lung metastasis of colon26-M3.1 cells. These data suggest that GF100 has antitumor activity to inhibit tumor metastasis prophylactically as well as therapeutically, and its antitumor effect is associated with activation of macrophages and NK cells.