| Autor: |
Malat P; Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand., Ekalaksananan T; Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand., Heawchaiyaphum C; Department of Biotechnology, Faculty of Science and Technology, Rangsit Center, Thammasart University, Pathum Thani 12120, Thailand., Suebsasana S; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Bangkok 10200, Thailand., Roytrakul S; Proteomics Research Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, Thailand., Yingchutrakul Y; Proteomics Research Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, Thailand., Pientong C; Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand. |
| Abstrakt: |
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. |
