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Article

Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA

by
Chen-Jei Tai
1,2,†,
Alagie Jassey
3,†,
Ching-Hsuan Liu
4,5,
Cheng-Jeng Tai
6,7,
Christopher D. Richardson
5,8,
Shu Hui Wong
9,10 and
Liang-Tzung Lin
4,11,*
1
Department of Traditional Chinese Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
2
Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
5
Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada
6
Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
7
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
8
Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, NS B3K 6R8, Canada
9
International Master Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
10
Institut de Recherches Cliniques de Montréal, Montreal, QC H2W 1R7, Canada
11
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
 
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*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Cells 2020, 9(4), 908; https://doi.org/10.3390/cells9040908
Submission received: 27 February 2020 / Revised: 3 April 2020 / Accepted: 7 April 2020 / Published: 8 April 2020
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Abstract

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.
Keywords: autophagy; berberine; biphasic cell death; ROS autophagy; berberine; biphasic cell death; ROS
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MDPI and ACS Style

Tai, C.-J.; Jassey, A.; Liu, C.-H.; Tai, C.-J.; Richardson, C.D.; Wong, S.H.; Lin, L.-T. Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA. Cells 2020, 9, 908. https://doi.org/10.3390/cells9040908

AMA Style

Tai C-J, Jassey A, Liu C-H, Tai C-J, Richardson CD, Wong SH, Lin L-T. Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA. Cells. 2020; 9(4):908. https://doi.org/10.3390/cells9040908

Chicago/Turabian Style

Tai, Chen-Jei, Alagie Jassey, Ching-Hsuan Liu, Cheng-Jeng Tai, Christopher D. Richardson, Shu Hui Wong, and Liang-Tzung Lin. 2020. "Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA" Cells 9, no. 4: 908. https://doi.org/10.3390/cells9040908

APA Style

Tai, C.-J., Jassey, A., Liu, C.-H., Tai, C.-J., Richardson, C. D., Wong, S. H., & Lin, L.-T. (2020). Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA. Cells, 9(4), 908. https://doi.org/10.3390/cells9040908

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