Expression of the anti-metastatic effect induced by Juzen-taiho-to is based on the content of Shimotsu-to constituents.
We investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, and its related formulations on the experimental liver and lung metastasis of tumor cells in vivo. Oral administration of Juzen-taiho-to for 7 d before tumor inoculation significantly reduced the number of liver metastatic colonies of colon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral administration for this same period before tumor inoculation also significantly inhibited lung metastasis of B16-BL6 melanoma cells. Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Shikunshi-to prescriptions together with two crude drugs (Cinnamomi Cortex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a significant reduction in the number of metastatic colonies and the liver weight as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect. Unsei-in containing four Shimotsu-to constituents was also active in inhibiting liver metastasis. Toki-shakuyaku-san and Ninjin-yoei-to, which include all Shimotsu-to constituents except Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, which contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably through an inhibitory mechanism different from Juzen-taiho-to. These results suggest that the anti-metastatic effect of Juzen-taiho-to is partly associated with its Shimotsu-to-derived constituents.
Department of Pathogenic Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Y
Y
Onishi
T
T
Yamaura
K
K
Tauchi
T
T
Sakamoto
K
K
Tsukada
S
S
Nunome
Y
Y
Komatsu
I
I
Saiki
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006131:Growth Inhibitors / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control / Q000556:secondary*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D006131:Growth Inhibitors; C063587:juzentaihoto; C079710:shimotsu-to