MC180295 Inhibited Epstein–Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which was disc...

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Published in:International journal of molecular sciences 2022-09, Vol.23 (18), p.10597
Main Authors: Fujii, Tomohiro, Nishikawa, Jun, Fukuda, Soichiro, Kubota, Naoto, Nojima, Junzo, Fujisawa, Koichi, Ogawa, Ryo, Goto, Atsushi, Hamabe, Koichi, Hashimoto, Shinichi, Wai, Aung Phyo, Iizasa, Hisashi, Yoshiyama, Hironori, Sakai, Kohei, Suehiro, Yutaka, Yamasaki, Takahiro, Takami, Taro
Format: Article
Language:English
Subjects:
Apoptosis
BRCA1 protein
BRCA2 protein
BZLF1 protein
Cdc45 protein
Cell cycle
Cell growth
Communication
Deoxyribonucleic acid
DNA
DNA damage
DNA methylation
DNA repair
Epigenetics
Epstein-Barr virus
Gastric cancer
Gene expression
Genes
Kinases
Repair
Serial analysis of gene expression
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Summary:DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which was discovered by screening for demethylating agents. MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with MC180295. MKN28 cells infected with EBV were sensitive to MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and MC180295 could up-regulate their expression. In conclusion, MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810597