T-Cell-Immunity-Based Inhibitory Effects of Orally Administered Herbal Medicine Juzen-taiho-to on the Growth of Primarily Developed Melanocytic Tumors in RET-Transgenic Mice

• Published in: Journal of investigative dermatology Vol. 117; no. 3; pp. 694 - 701
• Main Authors: Dai, Yan, Kato, Masashi, Takeda, Kozue, Kawamoto, Yoshiyuki, Akhand, Anwarul A., Hossain, Khaled, Suzuki, Haruhiko, Nakashima, Izumi
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Danvers, MA Elsevier Inc 01.09.2001; Nature Publishing; Elsevier Limited
• Subjects: Administration, Oral; Animals; Antineoplastic Agents - administration & dosage; antitumor immunity; Biological and medical sciences; Cells, Cultured; Drosophila Proteins; Drugs, Chinese Herbal - administration & dosage; General pharmacology; glycirrhizin; Immunity, Cellular; malignant melanoma; Medical sciences; Melanoma, Experimental - drug therapy; Melanoma, Experimental - genetics; Melanoma, Experimental - immunology; Mice; Mice, Transgenic; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - immunology; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - immunology; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - immunology; T-Lymphocytes - immunology; Asia; Japan; antitumor immunity; glycirrhizin; malignant melanoma; Rodentia; Melanocyte; Oral administration; Transgenic animal; Extract; Immunity; Biological activity; Vertebrata; Experimental disease; Mammalia; Folk medicine; Mouse; T-Lymphocyte; Plant origin; Tumor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.0022-202x.2001.01457.x

We examined the effect of oral administration of juzen-taiho-to, one of the most popular herbal medicines in Japan, on primary melanocytic tumor growth in RET-transgenic mice. There was virtually no difference between the lengths of tumor-free stages in the juzen-taiho-to-treated mice and the untreated littermate control mice. The rate of tumor growth in the juzen-taiho-to-treated mice, however, was greatly suppressed during the entire period after the initial tumor development. Correspondingly, the life span of juzen-taiho-to-treated transgenic mice was longer (over 6 mo in mean value) than that of control mice. We partially elucidated the mechanism of the antitumor effect of juzen-taiho-to. The addition of juzen-taiho-to at any of a wide range (50–1600 µg per ml) of concentrations to in vitro cultures of Mel-Ret cells, a malignant melanoma cell line derived from a RET-transgenic mouse, caused neither cell death nor cell cycle arrest directly. The addition of 50–400 µg per ml of juzen-taiho-to to cultures of murine spleen cells, however, promoted their DNA synthesis. More importantly, peritoneal exudate cells from the juzen-taiho-to-treated transgenic mice, in which the ratio and number of T cells were increased, displayed an antitumor immunity against Mel-Ret cells in vitro. Interestingly, the peritoneal-exudate-cell-associated antitumor immunity was further augmented by the addition of 200–400 µg per ml of juzen-taiho-to in vitro. This immunity, which was primarily conveyed by Thy-1+ T cells, was antigen (RET/melanoma) specific and cytotoxic. Amongst various chemical ingredients of juzen-taiho-to examined in this study, glycirrhizin displayed an action, partially replacing that of juzen-taiho-to, in promoting anti-Mel-Ret immunity when supplementarily added in vitro. These results suggest that juzen-taiho-to suppresses once-developed primary melanocytic tumors through potentiation of T-cell-mediated antitumor cytotoxic immunity in vivo.