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Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice

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. MET...

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Autores principales: Chou, Shun-Ting, Hsiang, Chien-Yun, Lo, Hsin-Yi, Huang, Hui-Fen, Lai, Ming-Tsung, Hsieh, Ching-Liang, Chiang, Su-Yin, Ho, Tin-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319192/
https://www.ncbi.nlm.nih.gov/pubmed/28219365
http://dx.doi.org/10.1186/s12906-017-1586-6
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author Chou, Shun-Ting
Hsiang, Chien-Yun
Lo, Hsin-Yi
Huang, Hui-Fen
Lai, Ming-Tsung
Hsieh, Ching-Liang
Chiang, Su-Yin
Ho, Tin-Yun
author_facet Chou, Shun-Ting
Hsiang, Chien-Yun
Lo, Hsin-Yi
Huang, Hui-Fen
Lai, Ming-Tsung
Hsieh, Ching-Liang
Chiang, Su-Yin
Ho, Tin-Yun
author_sort Chou, Shun-Ting
collection PubMed
description 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.
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spelling pubmed-53191922017-02-24 Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice Chou, Shun-Ting Hsiang, Chien-Yun Lo, Hsin-Yi Huang, Hui-Fen Lai, Ming-Tsung Hsieh, Ching-Liang Chiang, Su-Yin Ho, Tin-Yun BMC Complement Altern Med Research Article 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. BioMed Central 2017-02-20 /pmc/articles/PMC5319192/ /pubmed/28219365 http://dx.doi.org/10.1186/s12906-017-1586-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Chou, Shun-Ting
Hsiang, Chien-Yun
Lo, Hsin-Yi
Huang, Hui-Fen
Lai, Ming-Tsung
Hsieh, Ching-Liang
Chiang, Su-Yin
Ho, Tin-Yun
Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
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
title_full Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
title_fullStr Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
title_full_unstemmed Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
title_short Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
title_sort exploration of anti-cancer effects and mechanisms of zuo-jin-wan and its alkaloid components in vitro and in orthotopic hepg2 xenograft immunocompetent mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319192/
https://www.ncbi.nlm.nih.gov/pubmed/28219365
http://dx.doi.org/10.1186/s12906-017-1586-6
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