The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant melanoma primarily developed in ret-transgenic mice.
Sho-saiko-to is the most popular herbal medicine in Japan. We investigated the anti-tumor and anti-metastatic effects of Sho-saiko-to and its chemically defined ingredients on the primary skin melanoma that developed in a metallothionein-I (MT)/ret transgenic mouse line and on a melanoma cell line (Mel-ret), which was derived from a primary tumor developed in a MT/ret transgenic mouse. In vitro, Sho-saiko-to suppressed the growth of Mel-ret cells more strongly than any single ingredient of Sho-saiko-to, although baicalin as one of several ingredients tested also suppressed it significantly. In vivo, Sho-saiko-to (i) significantly (p < 0.02) prolonged the onset of tumor development (1.5 mo), (ii) definitely retarded the transition to malignancy, (iii) significantly decreased the incidence of distant metastasis to brain (p < 0.002), kidney (p < 0.05), and liver (p < 0.05) at the malignant stage, and (iv) significantly (p < 0.02) prolonged life span (2.6 mo). Moreover, Sho-saiko-to and baicalin down-regulated the matrix metalloproteinase-2 and -9 expression levels, and upregulated their inhibitor expression level in both the primary tumors and Mel-ret cells. In conclusion, Sho-saiko-to displayed anti-tumor and anti-metastatic effects on melanoma with regulation of the balance of matrix metalloproteinase and tissue inhibitor of the matrix metalloproteinase levels.
Department of Immunology, Nagoya University School of Medicine, Aichi, Japan.
M
M
Kato
W
W
Liu
H
H
Yi
N
N
Asai
A
A
Hayakawa
K
K
Kozaki
M
M
Takahashi
I
I
Nakashima
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D008545:Melanoma / Q000473:pathology* / Q000556:secondary*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019714:Tissue Inhibitor of Metalloproteinases
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D019714:Tissue Inhibitor of Metalloproteinases; C018142:saiko-keishi-to; D008666:Metalloendopeptidases