A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects

Xiao, Ji; Liu, Ping; Wang, Yiliang; Zhu, Yexuan; Zeng, Qian; Hu, Xiao; Ren, Zhe; Wang, Yifei

doi:10.3390/molecules27061973

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…When a ribose/deoxyribose group is attached to this molecule (Fig. 1a), it becomes two inhibitors for nucleic acid methylation (2), which can promote a variety of cellular stress responses such as apoptosis, autophagy and senescence (3,4). Meanwhile, they have been demonstrated to be functional as important chemotherapeutic drugs in the clinic treatment of myelodysplastic syndromes (MDS) (5) and acute myelogenous leukemia (2,5).…”

Section: Introductionmentioning

confidence: 99%

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†

Zi-wei

Wang

Jia

et al. 2022

Photochem & Photobiology

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Abstract5‐Azacytosine (5‐AC) is one of the best interesting noncanonical nucleobases due to its functionalization and structural imitation of natural bases. 5‐AC can be used as the scaffold of two important chemotherapeutic medicines, 5‐azacytidine and 2′‐deoxy‐5‐azacytidine. Furthermore, increased sensitivity to UV leads to the photochemical effects of 5‐AC also attracted attention. Yet, no study has been reported to explore the effect of glycosyl groups on the photophysical and photochemical properties of 5‐AC, which can help to reveal the photostability of related actual clinic drugs. In this study, the excited‐state dynamics of 5‐azacytidine and 2′‐deoxy‐5‐azacytidine are studied by femtosecond transient absorption and quantum‐chemical calculations while revisiting that of 5‐AC with a wider probe spectral range. It is shown that glycosyl substitution on the N1 position leads to ultrafast excited‐state relaxation within several picoseconds in both nucleosides, which is distinct compared with the 17 ps lifetime seen in 5‐AC. It is proposed that these changes are due to altering the energy level of the dark nπ* state. Moreover, our results suggest that it should be cautioned to simply replace sugar groups with methyl groups when doing a theoretical calculation study on nucleobases and their derivatives.

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Section: Introductionmentioning

confidence: 99%

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†

Zi-wei

Wang

Jia

et al. 2022

Photochem & Photobiology

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“…Decitabine may act as a nucleic acid drug, which has similar functions with anti-virus drugs. The research of Xiao J et al confirmed that decitabine showed potential antiviral activity by up-regulating the innate antiviral immune response (33).…”

Section: Discussionmentioning

confidence: 97%

Decitabine enhances the tumoricidal potential of TRAIL via the epigenetic regulation of death receptor 4 in gastric cancer

Niu

Zhu

et al. 2022

J Gastrointest Oncol

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Background: Deoxyribonucleic acid (DNA) methyltransferase inhibitors, such as decitabine, have made great advances in cancer therapy as combinational drugs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has an obvious anti-tumor effect; however, some gastric cancer (GC) cells are resistant to TRAIL-induced cell death. This study sought to explore the synergistic anti-tumor effect of TRAIL and decitabine, and the potential synergetic mechanism. Methods: The cell growth inhibition effect was monitored by the IncuCyte ZOOM Live-Cell Analysis System, and cell viability was determined by Cell Counting Kit-8 assays. Apoptosis was detected by Annexin V/Propidium Iodide double staining. Death receptor 4 (DR4) was knocked down by ribonucleic acid (RNA) interference, and the effect of DR4 deletion on TRAIL sensitivity was analyzed. Methylationspecific polymerase chain reaction (PCR) was applied to determine the methylation status of DR4. The messenger RNA (mRNA) and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The expression of the DRs on the cell membrane surfaces was analyzed by flow cytometry.Results: The combined use of decitabine and TRAIL synergistically inhibited cell growth in 2 TRAILresistant cell lines. Further, decitabine augmented TRAIL-induced apoptosis in a caspase-dependent manner.The co-application of decitabine and TRAIL facilitated the activation of caspase-7, -8, -9, and poly ADPribose polymerase (PARP). Notably, decitabine increased the expression of DR4 at the transcriptional and post-transcriptional levels. DR4 expression on the cell membrane surfaces was also upregulated after decitabine exposure. The depletion of DR4 by specific inhibitors attenuated TRAIL-induced apoptosis and weakened the synergistic effects of decitabine and TRAIL. In addition, DR4 gene presented methylation status in SNU-1 cells. The low mRNA and protein expression of DR4 were also detected in SNU-1 cells.Conclusions: Decitabine enhances the effect of TRAIL by inhibiting the growth and inducing the apoptosis of GC cells. This is achieved by the epigenetic modification of decitabine, which upregulates DR4. Decitabine may act as a sensitizing agent of TRAIL. The combined use of decitabine and TRAIL may provide a novel idea for GC treatment.

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“…Decitabine (DTB) has been identified as the most effective compound against EHV-4 in vitro. This compound is a deoxycytidine analog and hypomethylating agent used in the treatment of myelodysplastic syndromes [45,62]. In mice, the toxic concentration of decitabine was estimated to be 25 µM [63].…”

Section: Discussionmentioning

confidence: 99%

A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response

Normand,

Thieulent,

Fortier

et al. 2024

Viruses

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Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological disorders is not clearly demonstrated, there is a strong suspicion of its involvement. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of alpha-EHV infection still constitutes an important threat to the horse industry. Yet very few studies have been conducted on the search for antiviral molecules against EHV-4. A screening of 42 antiviral compounds was performed in vitro on equine fibroblast cells infected with the EHV-4 405/76 reference strain (VR2230). The formation of cytopathic effects was monitored by real-time cell analysis (RTCA), and the viral load was quantified by quantitative PCR. Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for eight molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine demonstrates the highest efficacy against EHV-4 in vitro. Transcriptomic analysis revealed the up-regulation of various genes implicated in interferon (IFN) response, suggesting that decitabine triggers the immune antiviral pathway.

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A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects

Cited by 7 publications

References 56 publications

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†

Decitabine enhances the tumoricidal potential of TRAIL via the epigenetic regulation of death receptor 4 in gastric cancer

A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response

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A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects

Cited by 7 publications

References 56 publications

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution†

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution†

Decitabine enhances the tumoricidal potential of TRAIL via the epigenetic regulation of death receptor 4 in gastric cancer

A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response

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Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†

Ribose and Deoxyribose Group Alter Excited‐State Dynamics of 5‐Azacytosine in Solution^†