Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins

Malat, Praphatson; Ekalaksananan, Tipaya; Heawchaiyaphum, Chukkris; Suebsasana, Supawadee; Roytrakul, Sittiruk; Yingchutrakul, Yodying; Pientong, Chamsai

doi:10.3390/molecules27144666

Cited by 5 publications

(6 citation statements)

References 39 publications

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“…Andrographolide inhibits EBV replication by inhibiting the expression of EBV lytic proteins, including Rta, Zta, and EA-D, during lytic activation in P3HR1 cells and thus inhibits the promoter activities of Zta and Rta [27]. Similarly, our previous study also demonstrated that andrographolide inhibits lytic gene expression and hinders the production of viral particles [28,29]. However, the underlying molecular mechanism through which andrographolide performs these functions in each type of epithelial malignancy is still unknown.…”

Section: Introductionmentioning

confidence: 93%

“…Our previous study demonstrated that andrographolide inhibits EBV lytic reactivation through the suppression of lytic protein expression and the inhibition of EBV virion production [28,29]. In this study, we further examined the inhibitory effect of andrographolide on the inhibition of EBV lytic reactivation in HNC cell lines via the treatment of EBV-positive HNC cell lines (HONE1-EBV, SCC25-EBV, and HSC1-EBV) with NaB alone, andrographolide alone, or andrographolide combined with NaB.…”

Section: Andrographolide Inhibits Ebv Lytic Reactivation In Hnc Cell ...mentioning

confidence: 99%

“…R PEER REVIEW 4 of 17 production [28,29]. In this study, we further examined the inhibitory effect of andrographolide on the inhibition of EBV lytic reactivation in HNC cell lines via the treatment of EBV-positive HNC cell lines (HONE1-EBV, SCC25-EBV, and HSC1-EBV) with NaB alone, andrographolide alone, or andrographolide combined with NaB.…”

Section: Andrographolide Inhibits Ebv Lytic Reactivation In Hnc Cell ...mentioning

confidence: 99%

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The Dual Functions of Andrographolide in the Epstein–Barr Virus-Positive Head-and-Neck Cancer Cells: The Inhibition of Lytic Reactivation of the Epstein–Barr Virus and the Induction of Cell Death

Heawchaiyaphum,

Malat,

Pientong

et al. 2023

IJMS

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Andrographolide, a medicinal compound, exhibits several pharmacological activities, including antiviral and anticancer properties. Previously, we reported that andrographolide inhibits Epstein–Barr virus (EBV) lytic reactivation, which is associated with viral transmission and oncogenesis in epithelial cancers, including head-and-neck cancer (HNC) cells. However, the underlying mechanism through which andrographolide inhibits EBV lytic reactivation and affects HNC cells is poorly understood. Therefore, we investigated these mechanisms using EBV-positive HNC cells and the molecular modeling and docking simulation of protein. Based on the results, the expression of EBV lytic genes and viral production were significantly inhibited in andrographolide-treated EBV-positive HNC cells. Concurrently, there was a reduction in transcription factors (TFs), myocyte enhancer factor-2D (MEF2D), specificity protein (SP) 1, and SP3, which was significantly associated with a combination of andrographolide and sodium butyrate (NaB) treatment. Surprisingly, andrographolide treatment also significantly induced the expression of DNA Methyltransferase (DNMT) 1, DNMT3B, and histone deacetylase (HDAC) 5 in EBV-positive cells. Molecular modeling and docking simulation suggested that HDAC5 could directly interact with MEF2D, SP1, and SP3. In our in vitro study, andrographolide exhibited a stronger cytotoxic effect on EBV-positive cells than EBV-negative cells by inducing cell death. Interestingly, the proteome analysis revealed that the expression of RIPK1, RIPK3, and MLKL, the key molecules for necroptosis, was significantly greater in andrographolide-treated cells. Taken together, it seems that andrographolide exhibits concurrent activities in HNC cells; it inhibits EBV lytic reactivation by interrupting the expression of TFs and induces cell death, probably via necroptosis.

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Section: Introductionmentioning

confidence: 93%

Section: Andrographolide Inhibits Ebv Lytic Reactivation In Hnc Cell ...mentioning

confidence: 99%

Section: Andrographolide Inhibits Ebv Lytic Reactivation In Hnc Cell ...mentioning

confidence: 99%

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The Dual Functions of Andrographolide in the Epstein–Barr Virus-Positive Head-and-Neck Cancer Cells: The Inhibition of Lytic Reactivation of the Epstein–Barr Virus and the Induction of Cell Death

Heawchaiyaphum,

Malat,

Pientong

et al. 2023

IJMS

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“…Furthermore, AGL greatly inhibited the 3Cpro's interferon (IFN) antagonistic effect by inhibiting the expression of interferon-stimulating genes (ISGs) [185]. AGL prevents EBV reactivation in EBV-positive cancer cells by suppressing EBV lytic genes, most likely via histone modifications such as H3-K9 modification and H3-K27 methylation [186]. AGL has been shown to prevent infections of DENV [184], ZIKV, and other arboviruses [187].…”

Section: Andrographolidementioning

confidence: 99%

“…Inhibits virus replications such HIV, HSV-1, HBV, HCV, ZIKV, DENV, CHIKV, FMDV, and IAV [181,182,184]. Prevents EBV reactivation by suppressing EBV lytic genes via histone modifications [186]. Also prevents IVA-induced inflammation through modulation of NF-κB and JAK-STAT signaling pathways [189].…”

Section: Apigeninmentioning

confidence: 99%

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

Gabbianelli,

Shahar,

de Simone

et al. 2023

Nutrients

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Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells’ epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field.

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