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Article: Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death
Title | Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death | ||||||||||
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Authors | |||||||||||
Keywords | Epithelial cancer Epstein-Barr virus Histone deacetylase inhibitor Lytic cycle Suberoylanilide hydroxamic acid | ||||||||||
Issue Date | 2010 | ||||||||||
Publisher | John 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? | ||||||||||
Abstract | In 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 Identifier | http://hdl.handle.net/10722/90481 | ||||||||||
ISSN | 2023 Impact Factor: 5.7 2023 SCImago Journal Rankings: 2.131 | ||||||||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Hui, KF | en_HK |
dc.contributor.author | Chiang, AKS | en_HK |
dc.date.accessioned | 2010-09-09T01:00:04Z | - |
dc.date.available | 2010-09-09T01:00:04Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | International Journal Of Cancer, 2010, v. 126 n. 10, p. 2479-2489 | en_HK |
dc.identifier.issn | 0020-7136 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/90481 | - |
dc.description.abstract | In 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.language | eng | - |
dc.publisher | John Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home | en_HK |
dc.relation.ispartof | International Journal of Cancer | en_HK |
dc.rights | International Journal of Cancer. Copyright © John Wiley & Sons, Inc. | - |
dc.subject | Epithelial cancer | en_HK |
dc.subject | Epstein-Barr virus | en_HK |
dc.subject | Histone deacetylase inhibitor | en_HK |
dc.subject | Lytic cycle | en_HK |
dc.subject | Suberoylanilide hydroxamic acid | en_HK |
dc.subject.mesh | Antineoplastic Agents - pharmacology | - |
dc.subject.mesh | Apoptosis - drug effects | - |
dc.subject.mesh | Carcinoma - drug therapy - virology | - |
dc.subject.mesh | Herpesvirus 4, Human - drug effects | - |
dc.subject.mesh | Histone Deacetylase Inhibitors - pharmacology | - |
dc.title | Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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.email | Chiang, AKS:chiangak@hkucc.hku.hk | en_HK |
dc.identifier.authority | Chiang, AKS=rp00403 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1002/ijc.24945 | en_HK |
dc.identifier.pmid | 19816947 | - |
dc.identifier.scopus | eid_2-s2.0-77951209628 | en_HK |
dc.identifier.hkuros | 170493 | - |
dc.identifier.hkuros | 183714 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77951209628&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 126 | en_HK |
dc.identifier.issue | 10 | en_HK |
dc.identifier.spage | 2479 | en_HK |
dc.identifier.epage | 2489 | en_HK |
dc.identifier.eissn | 1097-0215 | - |
dc.identifier.isi | WOS:000276928700021 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Hui, KF=35848529600 | en_HK |
dc.identifier.scopusauthorid | Chiang, AKS=7101623534 | en_HK |
dc.identifier.citeulike | 7070635 | - |
dc.identifier.issnl | 0020-7136 | - |