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Article: Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death

TitleSuberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death
Authors
KeywordsEpithelial cancer
Epstein-Barr virus
Histone deacetylase inhibitor
Lytic cycle
Suberoylanilide hydroxamic acid
Issue Date2010
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2010, v. 126 n. 10, p. 2479-2489 How to Cite?
AbstractIn Epstein-Barr virus (EBV)-associated malignancies, the virus is harbored in every tumor cell and persists in tightly latent forms expressing a very limited number of viral latent proteins. 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-positive 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-fold increase in viral DNA replication, strong expression of viral lytic proteins and production of infectious virus particles) and mediated enhanced cell death of EBV-positive AGS/BX1 cells when compared with that of EBV-negative 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-targeted drug for treatment of EBV-associated epithelial malignancies. © 2009 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/90481
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
Funding AgencyGrant Number
HKU-CRCG10207979
EBV Research20004525
HKU Studentship
Ho Tung Paediatrics Education and Research Fund
Funding Information:

Grant sponsor: HKU-CRCG; Grant number: 10207979; Grant sponsor: EBV Research; Grant number: 20004525; Grant sponsors: HKU Studentship, Ho Tung Paediatrics Education and Research Fund

References

 

DC FieldValueLanguage
dc.contributor.authorHui, KFen_HK
dc.contributor.authorChiang, AKSen_HK
dc.date.accessioned2010-09-09T01:00:04Z-
dc.date.available2010-09-09T01:00:04Z-
dc.date.issued2010en_HK
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 126 n. 10, p. 2479-2489en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90481-
dc.description.abstractIn Epstein-Barr virus (EBV)-associated malignancies, the virus is harbored in every tumor cell and persists in tightly latent forms expressing a very limited number of viral latent proteins. 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-positive 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-fold increase in viral DNA replication, strong expression of viral lytic proteins and production of infectious virus particles) and mediated enhanced cell death of EBV-positive AGS/BX1 cells when compared with that of EBV-negative 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-targeted drug for treatment of EBV-associated epithelial malignancies. © 2009 UICC.en_HK
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.-
dc.subjectEpithelial canceren_HK
dc.subjectEpstein-Barr virusen_HK
dc.subjectHistone deacetylase inhibitoren_HK
dc.subjectLytic cycleen_HK
dc.subjectSuberoylanilide hydroxamic aciden_HK
dc.subject.meshAntineoplastic Agents - pharmacology-
dc.subject.meshApoptosis - drug effects-
dc.subject.meshCarcinoma - drug therapy - virology-
dc.subject.meshHerpesvirus 4, Human - drug effects-
dc.subject.meshHistone Deacetylase Inhibitors - pharmacology-
dc.titleSuberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell deathen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=126&issue=10&spage=2479&epage=2489&date=2010&atitle=Suberoylanilide+hydroxamic+acid+induces+viral+lytic+cycle+in+Epstein-Barr+virus-positive+epithelial+malignancies+and+mediates+enhanced+cell+death-
dc.identifier.emailChiang, AKS:chiangak@hkucc.hku.hken_HK
dc.identifier.authorityChiang, AKS=rp00403en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ijc.24945en_HK
dc.identifier.pmid19816947-
dc.identifier.scopuseid_2-s2.0-77951209628en_HK
dc.identifier.hkuros170493-
dc.identifier.hkuros183714-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951209628&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume126en_HK
dc.identifier.issue10en_HK
dc.identifier.spage2479en_HK
dc.identifier.epage2489en_HK
dc.identifier.eissn1097-0215-
dc.identifier.isiWOS:000276928700021-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHui, KF=35848529600en_HK
dc.identifier.scopusauthoridChiang, AKS=7101623534en_HK
dc.identifier.citeulike7070635-

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