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Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo
While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this stud...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630794/ https://www.ncbi.nlm.nih.gov/pubmed/26525771 http://dx.doi.org/10.1038/srep16185 |
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author | Zhuo, Zhenjian Hu, Jianyang Yang, Xiaolin Chen, Minfen Lei, Xueping Deng, Lijuan Yao, Nan Peng, Qunlong Chen, Zhesheng Ye, Wencai Zhang, Dongmei |
author_facet | Zhuo, Zhenjian Hu, Jianyang Yang, Xiaolin Chen, Minfen Lei, Xueping Deng, Lijuan Yao, Nan Peng, Qunlong Chen, Zhesheng Ye, Wencai Zhang, Dongmei |
author_sort | Zhuo, Zhenjian |
collection | PubMed |
description | While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluated in vitro and in vivo. Mechanistic studies showed that ailanthone induced G(0)/G(1)-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG(1) phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer. |
format | Online Article Text |
id | pubmed-4630794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46307942015-11-16 Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo Zhuo, Zhenjian Hu, Jianyang Yang, Xiaolin Chen, Minfen Lei, Xueping Deng, Lijuan Yao, Nan Peng, Qunlong Chen, Zhesheng Ye, Wencai Zhang, Dongmei Sci Rep Article While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluated in vitro and in vivo. Mechanistic studies showed that ailanthone induced G(0)/G(1)-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG(1) phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer. Nature Publishing Group 2015-11-03 /pmc/articles/PMC4630794/ /pubmed/26525771 http://dx.doi.org/10.1038/srep16185 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhuo, Zhenjian Hu, Jianyang Yang, Xiaolin Chen, Minfen Lei, Xueping Deng, Lijuan Yao, Nan Peng, Qunlong Chen, Zhesheng Ye, Wencai Zhang, Dongmei Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title | Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title_full | Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title_fullStr | Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title_full_unstemmed | Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title_short | Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo |
title_sort | ailanthone inhibits huh7 cancer cell growth via cell cycle arrest and apoptosis in vitro and in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630794/ https://www.ncbi.nlm.nih.gov/pubmed/26525771 http://dx.doi.org/10.1038/srep16185 |
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