Anti-angiogenic and immunomodulatory effect of the herbal medicine "Juzen-taiho-to" on malignant glioma.
Juzen-taiho-to (JTT) is known as a Japanese herbal medicine that increases the immune function via the enhancement of phagocytosis, cytokine induction, and antibody production. Anti-neoplastic effects on malignant gliomas have been reported by means of the enhancement of the immune function in both animals and humans. We evaluated whether JTT has anti-angiogenic effects on malignant glioma growth in vitro and in vivo. In vitro, the anti-proliferative effect of JTT on malignant glioma cells and endothelial cells was assessed by cell proliferation assay. In vivo, a subcutaneous model of malignant glioma with different-aged mice (old, 43 weeks; young, 8 weeks) was used. After oral administration of JTT to mice, their immunological function and angiogenic status of tumor tissues were assessed by flow cytometry and immunohistochemistry, respectively. JTT inhibited human endothelial cell, but not glioma cell, proliferation in vitro. In vivo, the NK (natural killer) cell ratio within PBMC (peripheral blood mononuclear cells) and NK activity of fresh splenocytes obtained from JTT-treated old mice were significantly increased compared to the ratio and activity in control mice. In old mice, the vessel area of tumor tissues in JTT treatment groups was significantly decreased. These enhancements of immunological function and the inhibition of angiogenic activity were not observed in young mice. JTT not only increased host immunological function but also exerted anti-angiogenic effects on malignant glioma growth. JTT would be useful as an adjuvant medicine for malignant gliomas through its enhancement of systemic immunological function and its anti-angiogenic action.
Kamiyama
Hiroshi
H
Department of Neurosurgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
Takano
Shingo
S
Ishikawa
Eiichi
E
Tsuboi
Koji
K
Matsumura
Akira
A
D020533:Angiogenesis Inhibitors; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors; D019394:Ki-67 Antigen / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C063587:juzentaihoto