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Induction of EBV lytic cycle leads to expression of a much larger number of viral proteins, which may serve as potential therapeutic targets. We found that 4 histone deacetylase inhibitors, trichostatin A (TSA), sodium butyrate (SB), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), all significantly induced EBV lytic cycle in EBV\u2010positive gastric carcinoma cells (AGS\/BX1, latency II) but only weakly induced in Burkitt lymphoma cells (AK2003, latency I) and did not induce in lymphoblastoid cells (LCLs, latency III). Interestingly, SAHA potently induced viral lytic cycle in AGS\/BX1 cells at micromolar concentrations (evidenced by 8\u2010fold increase in viral DNA replication, strong expression of viral lytic proteins and production of infectious virus particles) and mediated enhanced cell death of EBV\u2010positive AGS\/BX1 cells when compared with that of EBV\u2010negative AGS cells, possibly related to cell cycle arrest at G2\/M phase. Furthermore, SAHA effected strong induction of EBV lytic cycle in nasopharyngeal carcinoma but not in NK lymphoma cells (both expressing EBV latency II pattern), indicating preferential viral lytic induction in epithelial rather than lymphoid malignancies. In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent, which warrants further investigation into its potential application as a novel virus\u2010targeted drug for treatment of EBV\u2010associated epithelial malignancies.<\/jats:p>","DOI":"10.1002\/ijc.24945","type":"journal-article","created":{"date-parts":[[2009,10,8]],"date-time":"2009-10-08T17:53:04Z","timestamp":1255024384000},"page":"2479-2489","source":"Crossref","is-referenced-by-count":67,"title":["Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein\u2010Barr virus\u2010positive epithelial malignancies and mediates enhanced cell death"],"prefix":"10.1002","volume":"126","author":[{"given":"K.F.","family":"Hui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan 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