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Conference Paper: Suberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinoma

TitleSuberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinoma
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010. How to Cite?
AbstractNasopharyngeal carcinoma (NPC) has uniquely high prevalence in Southern Chinese populations and a predilection to affect young adult males. Epstein-Barr virus (EBV) is harbored in every tumour cell of NPC but it persists in tightly latent form expressing few viral proteins and evading the immune system. Induction of EBV lytic cycle will lead to expression of a much larger number of viral proteins which may serve as potential therapeutic targets against the cancer. We reported that suberoylanilide hydroxamic acid (SAHA), a FDA-approved histone deacetylase inhibitor, could strongly induce viral lytic cycle in EBV-positive gastric carcinoma cells. Here, we demonstrated that SAHA (at 5-10 μM) could potently induce EBV lytic cycle in a panel of EBV-positive NPC cell lines, as evidenced by increased viral DNA replication, expression of immediate early (Zta and Rta), early (BMRF1) and late (VCA-p40 and gp350/220) viral lytic proteins and production of infectious viral particles. Immunofluorescent staining demonstrated expression of viral lytic proteins in more than 40% of the NPC cells. Enhanced killing of EBV-positive NPC cells when compared with that of EBV-negative counterparts was observed and cleaved form of PARP was predominantly expressed in EBV-positive than EBV-negative NPC cells, following treatment with SAHA for 24, 48 and 72 hours. The kinetics of expression of cleaved PARP correlated with that of Zta viral protein in EBV-positive NPC cells. In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent and mediates enhanced apoptosis of NPC cells. Further investigation into SAHA’s development as a novel virus-targeted therapeutic drug in NPC is warranted.
DescriptionPoster Session 23 - Epigenetic Modulators: abstract no. 5445
Persistent Identifierhttp://hdl.handle.net/10722/95213
ISSN

 

DC FieldValueLanguage
dc.contributor.authorHui, KFen_HK
dc.contributor.authorTsao, GSWen_HK
dc.contributor.authorChiang, AKSen_HK
dc.date.accessioned2010-09-25T15:55:11Z-
dc.date.available2010-09-25T15:55:11Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010.-
dc.identifier.issn1948-3279-
dc.identifier.urihttp://hdl.handle.net/10722/95213-
dc.descriptionPoster Session 23 - Epigenetic Modulators: abstract no. 5445-
dc.description.abstractNasopharyngeal carcinoma (NPC) has uniquely high prevalence in Southern Chinese populations and a predilection to affect young adult males. Epstein-Barr virus (EBV) is harbored in every tumour cell of NPC but it persists in tightly latent form expressing few viral proteins and evading the immune system. Induction of EBV lytic cycle will lead to expression of a much larger number of viral proteins which may serve as potential therapeutic targets against the cancer. We reported that suberoylanilide hydroxamic acid (SAHA), a FDA-approved histone deacetylase inhibitor, could strongly induce viral lytic cycle in EBV-positive gastric carcinoma cells. Here, we demonstrated that SAHA (at 5-10 μM) could potently induce EBV lytic cycle in a panel of EBV-positive NPC cell lines, as evidenced by increased viral DNA replication, expression of immediate early (Zta and Rta), early (BMRF1) and late (VCA-p40 and gp350/220) viral lytic proteins and production of infectious viral particles. Immunofluorescent staining demonstrated expression of viral lytic proteins in more than 40% of the NPC cells. Enhanced killing of EBV-positive NPC cells when compared with that of EBV-negative counterparts was observed and cleaved form of PARP was predominantly expressed in EBV-positive than EBV-negative NPC cells, following treatment with SAHA for 24, 48 and 72 hours. The kinetics of expression of cleaved PARP correlated with that of Zta viral protein in EBV-positive NPC cells. In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent and mediates enhanced apoptosis of NPC cells. Further investigation into SAHA’s development as a novel virus-targeted therapeutic drug in NPC is warranted.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Researchen_HK
dc.titleSuberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinomaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailHui, KF: fatboy6ling@yahoo.com.hken_HK
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_HK
dc.identifier.emailChiang, AKS: chiangak@hku.hken_HK
dc.identifier.authorityTsao, GSW=rp00399en_HK
dc.identifier.authorityChiang, AKS=rp00403en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros169987en_HK
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010.-

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