Immunopotentiation and antitumor effects of a ginsenoside Rg3-fortified red ginseng preparation in mice bearing H460 lung cancer cells

Antitumor effects of a ginsenoside Rg3-fortified red ginseng preparation (Rg3-RGP) were investigated in human non-small cell lung carcinoma (H460) cells using in vitro cytotoxicity assay and in vivo nude mouse xenograft model. Immunomodulatory effects of the preparation were also assessed by measuring the facilitating activities on the nitric oxide (NO) release from peritoneal macrophages, in vitro and in vivo lymphocyte proliferation, and the carbon clearance from circulating blood. In a cell level, Rg3-RGP exerted H460 cytotoxicity and facilitated splenocyte proliferation at very high concentrations, without affecting NO production. However, oral administration of Rg3-RGP (100–300 mg/kg) enhanced carbon particle-phagocytic index of blood macrophages up to 360–397% of control value. In addition, Rg3-RGP significantly increased the splenocyte proliferation (23% at 100 mg/kg). In tumor-bearing mice, 28-day oral treatment with Rg3-RGP (100 mg/kg) remarkably suppressed the tumor growth, leading to the decrease of the tumor volume and weight by 30–31%, which was comparable to the effect (27–29% reduction) of doxorubicin (2 mg/kg at 3-day intervals). While Rg3-RGP did not cause adverse effects, intravenous injection of doxorubicin markedly decreased body and testes weights, and exhibited severe depletion of spermatogenic cells in the atrophic seminiferous tubules. These results indicate that Rg3-RGP exerts antitumor activities via indirect immunomodulatory actions, without causing adverse effects as seen in doxorubicin.