Journal
MOLECULES
Volume 27, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/molecules27144666
Keywords
andrographolide; Epstein-Barr virus; lytic reactivation; BZLF1; histone modifications
Funding
- Faculty of Medicine, Khon Kaen University, Thailand [IN63111]
- Research and Graduate Studies, Khon Kaen University, Thailand [RP64-4/004]
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Andrographolide inhibits the reactivation of Epstein-Barr virus in EBV-positive cancer cells by inhibiting EBV lytic genes, possibly through histone modifications.
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.
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