Adenosine Induces EBV Lytic Reactivation through ADORA1 in EBV-Associated Gastric Carcinoma

species are known to contain numerous bioactive compounds, including cordycepin. Extracts of (CME) are used in diverse medicinal purposes because of their bioactive components. Cordycepin, one of the active components of CME, exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory effects....

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Bibliographic Details
Published in:International journal of molecular sciences 2019-03, Vol.20 (6), p.1286
Main Authors: Choi, Su Jin, Ryu, Eunhyun, Lee, Seulki, Huh, Sora, Shin, Yu Su, Kang, Byung Woog, Kim, Jong Gwang, Cho, Hyosun, Kang, Hyojeung
Format: Article
Language:English
Subjects:
Activation
Adenosine
BZLF1 protein
Cancer
Cell cycle
Experiments
Gastric cancer
Gene expression
Genomes
Infections
Kinases
Latency
Nucleoside analogs
Progeny
Proteins
Viral infections
Viruses
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Summary:species are known to contain numerous bioactive compounds, including cordycepin. Extracts of (CME) are used in diverse medicinal purposes because of their bioactive components. Cordycepin, one of the active components of CME, exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Cordycepin structurally differs from adenosine in that its ribose lacks an oxygen atom at the 3' position. We previously reported that cordycepin suppresses Epsteinā»Barr virus (EBV) gene expression and lytic replication in EBV-associated gastric carcinoma (EBVaGC). However, other studies reported that cordycepin induces EBV gene expression and lytic reactivation. Thus, it was reasonable to clarify the bioactive effects of CME bioactive compounds on the EBV life cycle. We first confirmed that CME preferentially induces EBV gene expression and lytic reactivation; second, we determined that adenosine in CME induces EBV gene expression and lytic reactivation; third, we discovered that the adenosine A1 receptor (ADORA1) is required for adenosine to initiate signaling for upregulating which encodes for a key EBV regulator (Zta) of the EBV lytic cycle; finally, we showed that upregulation by adenosine leads to delayed tumor development in the EBVaGC xenograft mouse model. Taken together, these results suggest that adenosine is an EBV lytic cycle inducer that inhibits EBVaGC development.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20061286