Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins
Reactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhi...
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MDPI AG
2022-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/14/4666 |
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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 | Reactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhibition of EBV lytic reactivation in EBV-positive cancer cells. The cytotoxicity of andrographolide was firstly evaluated in EBV-positive cancer cells; P3HR1, AGS-EBV and HONE1-EBV cells, using an MTT assay. Herein, the spontaneous expression of EBV lytic genes; BALF5, BRLF1 and BZLF1, was significantly inhibited in andrographolide-treated cells. Accordingly, andrographolide inhibited the expression of Zta and viral production in sodium butyrate (NaB)-induced EBV lytic reactivation. Additionally, proteomics and bioinformatics analysis revealed the differentially expressed proteins that inhibit EBV lytic reactivation in all treated cell lines were functionally related with the histone modifications and chromatin organization, such as histone H3-K9 modification and histone H3-K27 methylation. Taken together, andrographolide inhibits EBV reactivation in EBV-positive cancer cells by inhibiting EBV lytic genes, probably, through the histone modifications. |
| first_indexed | 2024-03-09T06:06:53Z |
| format | Article |
| id | doaj.art-fe1bbf384f2d4c358ce910cf84abac64 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T06:06:53Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-fe1bbf384f2d4c358ce910cf84abac642023-12-03T12:02:49ZengMDPI AGMolecules1420-30492022-07-012714466610.3390/molecules27144666Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related ProteinsPraphatson 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 Biotechnology, Faculty of Science and Technology, Rangsit Center, Thammasart University, Pathum Thani 12120, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Bangkok 10200, ThailandProteomics Research Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, ThailandProteomics Research Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandReactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhibition of EBV lytic reactivation in EBV-positive cancer cells. The cytotoxicity of andrographolide was firstly evaluated in EBV-positive cancer cells; P3HR1, AGS-EBV and HONE1-EBV cells, using an MTT assay. Herein, the spontaneous expression of EBV lytic genes; BALF5, BRLF1 and BZLF1, was significantly inhibited in andrographolide-treated cells. Accordingly, andrographolide inhibited the expression of Zta and viral production in sodium butyrate (NaB)-induced EBV lytic reactivation. Additionally, proteomics and bioinformatics analysis revealed the differentially expressed proteins that inhibit EBV lytic reactivation in all treated cell lines were functionally related with the histone modifications and chromatin organization, such as histone H3-K9 modification and histone H3-K27 methylation. Taken together, andrographolide inhibits EBV reactivation in EBV-positive cancer cells by inhibiting EBV lytic genes, probably, through the histone modifications.https://www.mdpi.com/1420-3049/27/14/4666andrographolideEpstein–Barr viruslytic reactivationBZLF1histone modifications |
| spellingShingle | Praphatson Malat Tipaya Ekalaksananan Chukkris Heawchaiyaphum Supawadee Suebsasana Sittiruk Roytrakul Yodying Yingchutrakul Chamsai Pientong Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins Molecules andrographolide Epstein–Barr virus lytic reactivation BZLF1 histone modifications |
| title | Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins |
| title_full | Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins |
| title_fullStr | Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins |
| title_full_unstemmed | Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins |
| title_short | Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins |
| title_sort | andrographolide inhibits epstein barr virus lytic reactivation in ebv positive cancer cell lines through the modulation of epigenetic related proteins |
| topic | andrographolide Epstein–Barr virus lytic reactivation BZLF1 histone modifications |
| url | https://www.mdpi.com/1420-3049/27/14/4666 |
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