Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice
Autor: | Su Yin Chiang, Tin-Yun Ho, Ming Tsung Lai, Hsin Yi Lo, Ching Liang Hsieh, Shun Ting Chou, Hui Fen Huang, Chien-Yun Hsiang |
---|---|
Jazyk: | angličtina |
Předmět: |
0301 basic medicine
Coptis chinensis Carcinoma Hepatocellular Berberine Pharmacology Xenograft mouse model Evodia 03 medical and health sciences chemistry.chemical_compound Alkaloids 0302 clinical medicine In vivo Evodiamine Animals Humans Cytotoxic T cell Medicine Bioluminescence imaging Medicine Chinese Traditional Mice Inbred ICR biology Anti-cancer business.industry Cell growth Zuo-Jin-Wan Hep G2 Cells General Medicine biology.organism_classification Antineoplastic Agents Phytogenic In vitro Evodia rutaecarpa 030104 developmental biology chemistry Complementary and alternative medicine 030220 oncology & carcinogenesis Quinazolines Heterografts Female business Coptis Drugs Chinese Herbal Phytotherapy Research Article |
Zdroj: | BMC Complementary and Alternative Medicine |
ISSN: | 1472-6882 |
DOI: | 10.1186/s12906-017-1586-6 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |