PMID- 29267216 OWN - NLM STAT- MEDLINE DCOM- 20180820 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 1 DP - 2017 Dec 21 TI - Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells. LID - 10.3390/ijms19010016 [doi] LID - 16 AB - 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. FAU - Tsai, Ching-Yi AU - Tsai CY AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. a07646815@yahoo.com.tw. FAU - Chen, Chang-Yu AU - Chen CY AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. chencyallen1689@gmail.com. FAU - Chiou, Yee-Hsuan AU - Chiou YH AD - Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 83102, Taiwan. chysn@ms6.hinet.net. FAU - Shyu, Huey-Wen AU - Shyu HW AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. shyuhw@hotmail.com. FAU - Lin, Kuan-Hua AU - Lin KH AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. su6473@mail2000.com.tw. FAU - Chou, Miao-Chen AU - Chou MC AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. miaochen119@gmail.com. FAU - Huang, Mei-Han AU - Huang MH AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. hmhmhtw8@gmail.com. FAU - Wang, Yi-Fen AU - Wang YF AD - Department of Medical Laboratory Science and Biotechnology, Fooyin-University, Kaohsiung 83102, Taiwan. sc071@fy.edu.tw. LA - eng PT - Journal Article DEP - 20171221 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antineoplastic Agents) RN - 0 (Antiviral Agents) RN - 0 (Reactive Oxygen Species) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) SB - IM MH - Antineoplastic Agents/pharmacology MH - Antiviral Agents/pharmacology MH - Apoptosis/*drug effects MH - Autophagy/*drug effects MH - Catechin/*analogs & derivatives/pharmacology/therapeutic use MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - HEK293 Cells MH - Herpesviridae Infections/complications/*drug therapy MH - Herpesvirus 8, Human/*drug effects MH - Humans MH - Lymphoma, Primary Effusion/*drug therapy/virology MH - Reactive Oxygen Species/*metabolism MH - Virus Replication/*drug effects PMC - PMC5795967 OTO - NOTNLM OT - EGCG OT - ROS OT - apoptosis OT - autophagy OT - primary effusion lymphoma COIS- The authors declare no conflict of interest. EDAT- 2017/12/22 06:00 MHDA- 2018/08/21 06:00 PMCR- 2018/01/01 CRDT- 2017/12/22 06:00 PHST- 2017/11/26 00:00 [received] PHST- 2017/12/15 00:00 [revised] PHST- 2017/12/18 00:00 [accepted] PHST- 2017/12/22 06:00 [entrez] PHST- 2017/12/22 06:00 [pubmed] PHST- 2018/08/21 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - ijms19010016 [pii] AID - ijms-19-00016 [pii] AID - 10.3390/ijms19010016 [doi] PST - epublish SO - Int J Mol Sci. 2017 Dec 21;19(1):16. doi: 10.3390/ijms19010016.