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DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells

DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug...

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Autores principales: Si, Ha, Genna, Ba, Zhuang, Xiangjin, Wang, Jing, Burenbatu, B., Feng, Qiyu, Wang, Hongyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161984/
https://www.ncbi.nlm.nih.gov/pubmed/32298294
http://dx.doi.org/10.1371/journal.pone.0231466
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author Si, Ha
Genna, Ba
Zhuang, Xiangjin
Wang, Jing
Burenbatu, B.
Feng, Qiyu
Wang, Hongyang
author_facet Si, Ha
Genna, Ba
Zhuang, Xiangjin
Wang, Jing
Burenbatu, B.
Feng, Qiyu
Wang, Hongyang
author_sort Si, Ha
collection PubMed
description DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy.
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spelling pubmed-71619842020-04-21 DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells Si, Ha Genna, Ba Zhuang, Xiangjin Wang, Jing Burenbatu, B. Feng, Qiyu Wang, Hongyang PLoS One Research Article DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy. Public Library of Science 2020-04-16 /pmc/articles/PMC7161984/ /pubmed/32298294 http://dx.doi.org/10.1371/journal.pone.0231466 Text en © 2020 Si et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Si, Ha
Genna, Ba
Zhuang, Xiangjin
Wang, Jing
Burenbatu, B.
Feng, Qiyu
Wang, Hongyang
DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title_full DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title_fullStr DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title_full_unstemmed DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title_short DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
title_sort dahuangwan targets egf signaling to inhibit the proliferation of hepatoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161984/
https://www.ncbi.nlm.nih.gov/pubmed/32298294
http://dx.doi.org/10.1371/journal.pone.0231466
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