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Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA
Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226840/ https://www.ncbi.nlm.nih.gov/pubmed/32276448 http://dx.doi.org/10.3390/cells9040908 |
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author | Tai, Chen-Jei Jassey, Alagie Liu, Ching-Hsuan Tai, Cheng-Jeng Richardson, Christopher D. Wong, Shu Hui Lin, Liang-Tzung |
author_facet | Tai, Chen-Jei Jassey, Alagie Liu, Ching-Hsuan Tai, Cheng-Jeng Richardson, Christopher D. Wong, Shu Hui Lin, Liang-Tzung |
author_sort | Tai, Chen-Jei |
collection | PubMed |
description | Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main type of cell death elicited by BBR, and whether the alkaloid can inhibit hepatoma cells carrying HCV genomes, is unclear. Herein, we show that BBR treatment induced a biphasic cell death irrespective of the presence of HCV subgenomic replicon RNA, first triggering apoptosis that then progressed to necrosis between 24 and 48 h post-treatment. Furthermore, BBR treatment potentiated the HCV replicon-induced reactive oxygen species (ROS) production, inhibition of which with an antioxidant attenuated the cell death that was elicited by BBR in these cells. Moreover, BBR dampened the autophagic response in HCV RNA-positive or negative hepatoma cells, and pharmacological inhibition of autophagy conversely augmented the BBR-induced cell death. Finally, BBR inhibited the growth of Huh-7 cells that were persistently infected with the full-length genome HCV particles, and concomitant pharmacological inhibition of autophagy potentiated the killing of these cells by BBR. Our findings suggest that combining BBR with the inhibition of autophagy could be an attractive treatment strategy against HCC, irrespective of the presence of the HCV genome. |
format | Online Article Text |
id | pubmed-7226840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72268402020-05-18 Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA Tai, Chen-Jei Jassey, Alagie Liu, Ching-Hsuan Tai, Cheng-Jeng Richardson, Christopher D. Wong, Shu Hui Lin, Liang-Tzung Cells Article Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main type of cell death elicited by BBR, and whether the alkaloid can inhibit hepatoma cells carrying HCV genomes, is unclear. Herein, we show that BBR treatment induced a biphasic cell death irrespective of the presence of HCV subgenomic replicon RNA, first triggering apoptosis that then progressed to necrosis between 24 and 48 h post-treatment. Furthermore, BBR treatment potentiated the HCV replicon-induced reactive oxygen species (ROS) production, inhibition of which with an antioxidant attenuated the cell death that was elicited by BBR in these cells. Moreover, BBR dampened the autophagic response in HCV RNA-positive or negative hepatoma cells, and pharmacological inhibition of autophagy conversely augmented the BBR-induced cell death. Finally, BBR inhibited the growth of Huh-7 cells that were persistently infected with the full-length genome HCV particles, and concomitant pharmacological inhibition of autophagy potentiated the killing of these cells by BBR. Our findings suggest that combining BBR with the inhibition of autophagy could be an attractive treatment strategy against HCC, irrespective of the presence of the HCV genome. MDPI 2020-04-08 /pmc/articles/PMC7226840/ /pubmed/32276448 http://dx.doi.org/10.3390/cells9040908 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tai, Chen-Jei Jassey, Alagie Liu, Ching-Hsuan Tai, Cheng-Jeng Richardson, Christopher D. Wong, Shu Hui Lin, Liang-Tzung Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title | Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title_full | Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title_fullStr | Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title_full_unstemmed | Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title_short | Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA |
title_sort | targeting autophagy augments berberine-mediated cell death in human hepatoma cells harboring hepatitis c virus rna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226840/ https://www.ncbi.nlm.nih.gov/pubmed/32276448 http://dx.doi.org/10.3390/cells9040908 |
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