title: Antitumor Activity of the Chinese Medicine JC-001 Is Mediated by Immunomodulation in a Murine Model of Hepatocellular Carcinoma.
abstract: JC-001 is a Chinese medicine that has been used to treat liver disease; however, its significance in cancer treatment has not been characterized. In this study, we used an immunocompetent tumor model to characterize the antitumor activity of JC-001. A total of 48 Hepa 1-6 tumor-bearing C57BL/6 mice were randomly grouped into 4 groups and treated with H2O or JC-001 via oral administration. After hepatoma cell lines, including HepG2, Hep3B, SK-Hep-1, and Hepa 1-6, underwent 96 hours of JC-001 treatment, a low cytotoxic effect was observed. In contrast, no direct cytotoxic effect of JC-001 on a normal human liver cell line, THLE-3, was observed under the same incubation conditions. Using a murine tumor model, we found that tumor growth could be inhibited by JC-001 in C57BL/6 mice but not in immunodeficient mice. Histopathological analysis of tumors from C57BL/6 mice revealed immune cell infiltration in tumors from the JC-001-treated group, as observed by hematoxylin and eosin staining; in addition, Ki67, hypoxia-inducible factor-1-α, and high mobility group box 1 expression levels were suppressed in the tumors. Both the coculture assay and murine spleen mRNA quantitative PCR analyses demonstrated that JC-001 could suppress Th17 immunity. Our data suggest that JC-001 is a Chinese medicine with low cytotoxicity that can significantly suppress tumor growth by immune regulation. This herbal remedy has great potential for future clinical application in hepatoma therapy.
authors.affiliation: 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Meng-Hsien
authors.initials: MH
authors.lastname: Chuang
authors.affiliation: 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|2 Department of Chest Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jinghua Tsai
authors.initials: JT
authors.lastname: Chang
authors.affiliation: 3 Department of Medical Laboratory Science and Technology, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Hsu
authors.affiliation: 4 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|5 Immunology Research Center, Chung Shan Medical University, Taichung,Taiwan.|6 Division of Allergy, Immunology and Rheumatology, Department ofInternal Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Jan
authors.affiliation: 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|7 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Fung-Jou
authors.initials: FJ
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D024002:HMGB Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D024002:HMGB Proteins; D012333:RNA, Messenger
keywords: Chinese medicine; Hepa 1-6; JC-001; coculture; hepatocellular carcinoma; immunomodulation; splenocytes