Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir.
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.
Jung
Eun Ji
EJ
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Lee
You Mie
YM
Lee
Byung Lan
BL
Chang
Mee Soo
MS
Kim
Woo Ho
WH
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
D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine; D015774:Ganciclovir