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Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8...

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Autores principales: Tsai, Ching-Yi, Chen, Chang-Yu, Chiou, Yee-Hsuan, Shyu, Huey-Wen, Lin, Kuan-Hua, Chou, Miao-Chen, Huang, Mei-Han, Wang, Yi-Fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795967/
https://www.ncbi.nlm.nih.gov/pubmed/29267216
http://dx.doi.org/10.3390/ijms19010016
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author Tsai, Ching-Yi
Chen, Chang-Yu
Chiou, Yee-Hsuan
Shyu, Huey-Wen
Lin, Kuan-Hua
Chou, Miao-Chen
Huang, Mei-Han
Wang, Yi-Fen
author_facet Tsai, Ching-Yi
Chen, Chang-Yu
Chiou, Yee-Hsuan
Shyu, Huey-Wen
Lin, Kuan-Hua
Chou, Miao-Chen
Huang, Mei-Han
Wang, Yi-Fen
author_sort Tsai, Ching-Yi
collection PubMed
description Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS) generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs) activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC) inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas.
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spelling pubmed-57959672018-02-09 Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells Tsai, Ching-Yi Chen, Chang-Yu Chiou, Yee-Hsuan Shyu, Huey-Wen Lin, Kuan-Hua Chou, Miao-Chen Huang, Mei-Han Wang, Yi-Fen Int J Mol Sci Article Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS) generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs) activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC) inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas. MDPI 2017-12-21 /pmc/articles/PMC5795967/ /pubmed/29267216 http://dx.doi.org/10.3390/ijms19010016 Text en © 2017 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
Tsai, Ching-Yi
Chen, Chang-Yu
Chiou, Yee-Hsuan
Shyu, Huey-Wen
Lin, Kuan-Hua
Chou, Miao-Chen
Huang, Mei-Han
Wang, Yi-Fen
Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title_full Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title_fullStr Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title_full_unstemmed Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title_short Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells
title_sort epigallocatechin-3-gallate suppresses human herpesvirus 8 replication and induces ros leading to apoptosis and autophagy in primary effusion lymphoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795967/
https://www.ncbi.nlm.nih.gov/pubmed/29267216
http://dx.doi.org/10.3390/ijms19010016
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