Juzen-Taiho-To (JTT) is well known to be one of
Kampo (Japanese herbal) medicine consisted of 10 component herbs and used for the supplemental
therapy of
cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of
cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of
cancer metastasis using experimental mouse model. JTT was well mixed with rodent chow at concentrations of either 0.2 or 1.0%, and administered orally ad libitum, which was started 1 week before
tumor cell injection and continue throughout the experiment.
Oral administration of JTT at concentration 0.2 and 1.0% into C57BL/6 male mice significantly inhibited
tumor metastasis in lungs, which was induced by the
intravenous injection of 2 × 10(5)
B16 melanoma cell. JTT at a concentration of 1.0% also significantly suppressed lung
metastasis of
B16 melanoma cell from hind footpad in C57BL/6 mice. In the second part of experiments, the influence of the depression of natural killer (NK) cell, natural killer T (NKT) cell and several types of
cytokines on JTT-mediated inhibition of
tumor cell
metastasis.
Intraperitoneal injection of anti asialo-GM1 antibody against NK cells and anti NK-1.1
monoclonal antibody (mAb) to NKT cells abrogated the inhibitory action of JTT on lung
metastasis of
B16 melanoma cells. Although intraperitoneal administration of anti-IFN-γ mAb scarcely affected the inhibitory action of JTT on
tumor cell
metastasis, injection of
amrinone, which used for
IL-12 suppression, significantly decreased the ability of JTT to prevent
tumor cell
metastasis. These results strongly suggest that
oral administration of JTT caused increase in the production of
IL-12, which is responsible for the activation of both NK cell and NKT cell, in the lungs and results in inhibition of
B16 melanoma cell
metastasis in the lungs.