title: Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir.
abstract: Epstein-Barr virus (EBV) is an oncogenic herpes virus. EBV gene transcription is regulated by an epigenetic mechanism to establish a persistent infection and to evade the host immune system. We found that low concentrations of epigenetic modifying agents, 5-aza-2'-deoxycytidine (5-aza-CdR) or trichostatin A (TSA), induced the expression of BMRF1, BZLF1, and BRLF1 genes, which are found in the lytic form of the virus, in an EBV-positive gastric cancer cell line. This effect did not involve PI3 kinase, MAP/ERK kinase, protein kinase C delta, or p38 MAPK signaling pathway. The cytotoxic effect of ganciclovir (GCV) was enhanced after the lytic induction by epigenetic modifiers, and the combination of GCV and epigenetic modifiers induced apoptosis, which is dependent on caspases. In conclusion, the combination of GCV with 5-aza-CdR or TSA might be a useful therapeutic strategy for EBV-induced human gastric cancer.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jung
authors.forename: You Mie
authors.initials: YM
authors.lastname: Lee
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000494:pharmacology; D000077209:Decitabine; D015774:Ganciclovir / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000821:virology*; D014775:Virus Activation
chemical_list: D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine; D015774:Ganciclovir