title: Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice.
abstract: BACKGROUND
  Zuo-Jin-Wan (ZJW), a two-herb formula consisting of Coptis chinensis (CC) and Evodia rutaecarpa (ER), is commonly used in traditional Chinese medicine for the treatment of cancers. However, the efficacies and mechanisms of ZJW and its alkaloid components on cancers are still unclear.
  
  
  METHODS
  Here we investigated the anti-cancer effects and mechanisms of ZJW, CC, ER, berberine, and evodiamine in cells and in intrahepatic xenograft mice.
  
  
  RESULTS
  Treatment of HepG2 cells with ZJW, CC, ER, berberine, and evodiamine significantly displayed cytotoxic effects in a dose- and time-dependent manner. Hierarchical cluster analysis of gene expression profiles showed that CC and ZJW shared a similar mechanism for the cytotoxic effects, suggesting that CC was the active ingredient of ZJW for anti-cancer activity. Network analysis further showed that c-myc was the likely key molecule involved in the regulation of ZJW-affected gene expression. A human hepatoma xenograft model was established by intrahepatic injection of HepG2 cells containing nuclear factor-κB-driven luciferase genes in immunocompetent mice. In vivo bioluminescence imaging showed that cells had been successfully transplanted in mouse liver. Oral administration of ZJW for 28 consecutive days led to a significant decrease in the accumulation of ascites, the ratio of tumor-to-liver, and the number of transplanted cells in livers.
  
  
  CONCLUSIONS
  In conclusion, our findings suggested for the first time that ZJW significantly suppressed human cancer cell growth in orthotopic HepG2 xenograft-bearing immunocompetent mice. Moreover, c-myc might play a potent role in the cytotoxic mechanisms of ZJW, CC, ER, berberine, and evodiamine.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Shun-Ting
authors.initials: ST
authors.lastname: Chou
authors.affiliation: Department of Microbiology, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Chien-Yun
authors.initials: CY
authors.lastname: Hsiang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lo
authors.affiliation: School of Post-baccalaureate Chinese Medicine, Tzu Chi University, Hualien, 97004, Taiwan.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Huang
authors.affiliation: School of Medicine, Chung-Shan Medical University, Taichung, 40201, Taiwan.|Department of Pathology, Chung-Shan Medical University Hospital, Taichung, 40201, Taiwan.
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Lai
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40402, Taiwan.|Department of Chinese Medicine, China Medical University Hospital, Taichung, 40447, Taiwan.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. sychiang@mail.cmu.edu.tw.
authors.forename: Su-Yin
authors.initials: SY
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. tyh@mail.cmu.edu.tw.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan. tyh@mail.cmu.edu.tw.
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D039323:Coptis / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D032086:Evodia / Q000737:chemistry*; D005260:Female; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008516:Medicine, Chinese Traditional; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D011799:Quinazolines; C560510:Zuo-Jin-Wan; D001599:Berberine; C049639:evodiamine
keywords: Anti-cancer; Coptis chinensis; Evodia rutaecarpa; Xenograft mouse model; Zuo-Jin-Wan