Keishi-ka-kei-to, a Traditional Chinese Herbal Medicine, Inhibits Pulmonary Metastasis of B16 Melanoma

Keishi-ka-kei-to, a traditional Chinese herbal medicine composed of a mixture of crude extracts from five medicinal plants (Cinnamomi cortex, Paeoniae radix, Zizyphi fructus, Zingiberis rhizoma and Glycyrrhizae radix), inhibited experimental pulmonary metastasis in mice implanted with B16F10 melanoma cells. When 136 to 145 metastatic colonies were produced in lungs of mice inoculated with 1 x 10(5) cells/mouse of melanoma cells, less than 15 metastatic colonies were demonstrated when these tumor-inoculated mice were treated orally with 80 to 320 mg/kg doses of Keishi-ka-kei-to. The most active component in the mixture was shown to be 6-gingerol, derived from the Zingiberis rhizoma extract. The antimetastatic activity of 6-gingerol was expressed through the host's antitumor immune functions, as the growth of B16F10 melanoma cells was not affected by this substance in vitro. The splenic CD8+ T cells from mice treated with the compound showed inhibitory activities on pulmonary metastasis when these T cells were adoptively transferred to mice bearing B16F10 melanoma cells. These results may suggest that Keishi-ka-kei-to inhibits pulmonary metastasis in mice bearing B16F10 melanoma cells through the stimulation of CD8+ T cells.