The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant melanoma primarily developed in ret-transgenic mice

M. Kato, W. Liu, H. Yi, N. Asai, A. Hayakawa, K. I. Kozaki, M. Takahashi, I. Nakashima

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 antimetastatic effects on melanoma with regulation of the balance of matrix metalloproteinase and tissue inhibitor of the matrix metalloproteinase levels.

Original languageEnglish
Pages (from-to)640-644
Number of pages5
JournalJournal of Investigative Dermatology
Volume111
Issue number4
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Herbal Medicine
Transgenic Mice
Melanoma
Neoplasm Metastasis
Tumors
Growth
Neoplasms
Metallothionein
Cells
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
shosaiko-to
Matrix Metalloproteinases
Liver
Brain
Skin
Japan
Tissue

Keywords

  • Baicalin
  • Matrix metalloproteinase
  • Sho-saiko-to

ASJC Scopus subject areas

  • Dermatology

Cite this

The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant melanoma primarily developed in ret-transgenic mice. / Kato, M.; Liu, W.; Yi, H.; Asai, N.; Hayakawa, A.; Kozaki, K. I.; Takahashi, M.; Nakashima, I.

In: Journal of Investigative Dermatology, Vol. 111, No. 4, 1998, p. 640-644.

Research output: Contribution to journalArticle

Kato, M. ; Liu, W. ; Yi, H. ; Asai, N. ; Hayakawa, A. ; Kozaki, K. I. ; Takahashi, M. ; Nakashima, I. / The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant melanoma primarily developed in ret-transgenic mice. In: Journal of Investigative Dermatology. 1998 ; Vol. 111, No. 4. pp. 640-644.
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N2 - 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 antimetastatic effects on melanoma with regulation of the balance of matrix metalloproteinase and tissue inhibitor of the matrix metalloproteinase levels.

AB - 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 antimetastatic effects on melanoma with regulation of the balance of matrix metalloproteinase and tissue inhibitor of the matrix metalloproteinase levels.

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