The present study investigated the preventive effect of Saiboku-to, a Chinese herbal medicine, upon chemically induced carinogenesis in mice, and analyzed the mechanism of effect. Saiboku-to was orally administered to C3H/HeJ mice in a daily dose of 100mg/kg or 1000mg/kg in each of two groups. Six weeks after initiating Saiboku-to administration, mice were subcutaneously injected with a tumorigenic dose (1mg/mouse) of 3-methylcholanthrene (MC) and tumor development was observed for 25 weeks. In control mice, the incidence of tumor was 40% 10 weeks after MC injection. However, the tumor incidence in Saiboku-to treated mice was only a few percent 10 weeks after MC injection. A tumor incidence of 40% in Saiboku-to treated mice was reached about 18 weeks after MC injection, showing the delaying effect of Saiboku-to on carcinognesis. Therefore, a delaying effect on carcinogenesis was observed in Saiboku-to treated mice, although all mice had tumors within 23 weeks after MC injection. The mechanism of the delay in carcinogenesis was investigated by depletion of NK cells, T cells and macrophages in vivo, respectively. The delay of carcinogenesis disappeared after using anti-asialo-GM1 antibody, anti-thymocyte antibody, and carrageenan in Saiboku-to treated mice, showing that NK cells, T cells, and macrophages play an important role in delaying by Saiboku-to administration in experimental carcinogenesis.
Moreover, prior treatment for 6 weeks with Saiboku-to significantly enhanced the NK cell activity of splenic cells and the cytotoxity and lysosomal enzyme activities (acid Phosphatase, beta-galactosidase) of peritoneal macrophages in normal mice. These augmentations were suppressed using anti-asialo GM1 antibody or carrageenan in vivo. Thus, Saiboku-to showed prophylactic effect on chemical carcinogenesis, suggesting activa-tion of the immune status of the host.