Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir

Cancer Letters
Eun Ji JungWoo Ho Kim

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.

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Citations

Apr 4, 2013·Current Treatment Options in Oncology·Jennifer A Kanakry, Richard F Ambinder
Jun 4, 2010·Pathology International·Masashi Fukayama
Jan 5, 2011·Infectious Agents and Cancer·Julie L RyanMargaret L Gulley
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Aug 5, 2018·Journal of Cellular Physiology·Sadegh FattahiHaleh Akhavan-Niaki
Mar 7, 2012·Journal of Clinical Gastroenterology·Jian-Ning ChenChun-Kui Shao
May 26, 2017·Journal of Gynecologic Oncology·Yaw Wen HsuHung Cheng Lai
Jul 5, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maarten A WildemanAstrid E Greijer

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