Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer
Andrographolide is the principal bioactive chemical constituent of <i>Andrographis paniculata</i> and exhibits activity against several viruses, including Epstein–Barr virus (EBV). However, the particular mechanism by which andrographolide exerts an anti-EBV effect in EBV-associated gast...
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MDPI AG
2021-12-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/12/2561 |
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| author | Praphatson Malat Tipaya Ekalaksananan Chukkris Heawchaiyaphum Supawadee Suebsasana Sittiruk Roytrakul Yodying Yingchutrakul Chamsai Pientong |
| author_facet | Praphatson Malat Tipaya Ekalaksananan Chukkris Heawchaiyaphum Supawadee Suebsasana Sittiruk Roytrakul Yodying Yingchutrakul Chamsai Pientong |
| author_sort | Praphatson Malat |
| collection | DOAJ |
| description | Andrographolide is the principal bioactive chemical constituent of <i>Andrographis paniculata</i> and exhibits activity against several viruses, including Epstein–Barr virus (EBV). However, the particular mechanism by which andrographolide exerts an anti-EBV effect in EBV-associated gastric cancer (EBVaGC) cells remains unclear. We investigated the molecular mechanism by which andrographolide inhibits lytic reactivation of EBV in EBVaGC cells (AGS-EBV cell line) using proteomics and bioinformatics approaches. An andrographolide treatment altered EBV protein-expression patterns in AGS-EBV cells by suppressing the expression of EBV lytic protein. Interestingly cellular transcription factors (TFs), activators for EBV lytic reactivation, such as MEF2D and SP1, were significantly abolished in AGS-EBV cells treated with andrographolide and sodium butyrate (NaB) compared with NaB-treated cells. In contrast, the suppressors of EBV lytic reactivation, such as EZH2 and HDAC6, were significantly up-regulated in cells treated with both andrographolide and NaB compared with NaB treatment alone. In addition, bioinformatics predicted that HDAC6 could interact directly with MEF2D and SP1. Furthermore, andrographolide significantly induced cell cytotoxicity and apoptosis of AGS-EBV cells by induction of apoptosis-related protein expression. Our results suggest that andrographolide inhibits EBV lytic reactivation by inhibition of host TFs, partially through the interaction of HDAC6 with TFs, and induces apoptosis of EBVaGC cells. |
| first_indexed | 2024-03-10T03:31:16Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T03:31:16Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-556c19201a7540739e2923c3bb743c902023-11-23T09:39:53ZengMDPI AGMicroorganisms2076-26072021-12-01912256110.3390/microorganisms9122561Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric CancerPraphatson Malat0Tipaya Ekalaksananan1Chukkris Heawchaiyaphum2Supawadee Suebsasana3Sittiruk Roytrakul4Yodying Yingchutrakul5Chamsai Pientong6Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Bangkok 10200, ThailandGenome Technology Research Unit, Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, ThailandGenome Technology Research Unit, Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandAndrographolide is the principal bioactive chemical constituent of <i>Andrographis paniculata</i> and exhibits activity against several viruses, including Epstein–Barr virus (EBV). However, the particular mechanism by which andrographolide exerts an anti-EBV effect in EBV-associated gastric cancer (EBVaGC) cells remains unclear. We investigated the molecular mechanism by which andrographolide inhibits lytic reactivation of EBV in EBVaGC cells (AGS-EBV cell line) using proteomics and bioinformatics approaches. An andrographolide treatment altered EBV protein-expression patterns in AGS-EBV cells by suppressing the expression of EBV lytic protein. Interestingly cellular transcription factors (TFs), activators for EBV lytic reactivation, such as MEF2D and SP1, were significantly abolished in AGS-EBV cells treated with andrographolide and sodium butyrate (NaB) compared with NaB-treated cells. In contrast, the suppressors of EBV lytic reactivation, such as EZH2 and HDAC6, were significantly up-regulated in cells treated with both andrographolide and NaB compared with NaB treatment alone. In addition, bioinformatics predicted that HDAC6 could interact directly with MEF2D and SP1. Furthermore, andrographolide significantly induced cell cytotoxicity and apoptosis of AGS-EBV cells by induction of apoptosis-related protein expression. Our results suggest that andrographolide inhibits EBV lytic reactivation by inhibition of host TFs, partially through the interaction of HDAC6 with TFs, and induces apoptosis of EBVaGC cells.https://www.mdpi.com/2076-2607/9/12/2561andrographolideEBVEBV lytic reactivationtranscriptional factorMEF2DSP1 |
| spellingShingle | Praphatson Malat Tipaya Ekalaksananan Chukkris Heawchaiyaphum Supawadee Suebsasana Sittiruk Roytrakul Yodying Yingchutrakul Chamsai Pientong Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer Microorganisms andrographolide EBV EBV lytic reactivation transcriptional factor MEF2D SP1 |
| title | Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer |
| title_full | Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer |
| title_fullStr | Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer |
| title_full_unstemmed | Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer |
| title_short | Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer |
| title_sort | andrographolide inhibits lytic reactivation of epstein barr virus by modulating transcription factors in gastric cancer |
| topic | andrographolide EBV EBV lytic reactivation transcriptional factor MEF2D SP1 |
| url | https://www.mdpi.com/2076-2607/9/12/2561 |
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