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Conference Paper: Combination of histone deacetylase and proteasome inhibitors induces enhanced killing of Epstein-Barr virus-positive lymphoblastoid cells through suppression of the function of EBNA-3c protein

TitleCombination of histone deacetylase and proteasome inhibitors induces enhanced killing of Epstein-Barr virus-positive lymphoblastoid cells through suppression of the function of EBNA-3c protein
Authors
Issue Date2015
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH
Citation
The International Symposium on Childhood, Adolescent and. Young Adult Non-Hodgkin Lymphoma, Varese, Italy, 21-24 October 2015. In British Journal of Haematology, 2015, v. 171 suppl. S1, p. 38, abstract no. 65 How to Cite?
AbstractBACKGROUND: Epstein-Barr virus (EBV) drives the development of post-transplant lymphoproliferative disorder (PTLD) via the concerted action of Epstein-Barr nuclear antigen (EBNA) proteins. We previously reported that combination of histone deacetylase inhibitor (HDACI) and proteasome inhibitor (PI) could synergistically induce apoptosis of lymphoblastoid cells (LCLS), an in-vitro cell model of PTLD, which express the EBNA-3A, -3B and -3C proteins. OBJECTIVES: We aim to investigate whether combination of HDACI and PI induces apoptosis of LCLs by suppressing the function of EBNA-3A, -3B or -3C protein. Design/Methods: Spontaneous LCLs and a panel of B cell lines harboring EBNA-3A, -3B or -3C knockout EBV genome and corresponding cell lines harboring the knockout virus together with the individual gene revertant were treated with combination of HDACI (vorinostat) and PI (bortezomib), followed by analyses of apoptosis and cell cycle. In-vivo testing of B cell xenografts in SCID mice was also performed. RESULTS: MTT assay showed that vorinostat/bortezomib induced enhanced cell death in EBNA-3C expressing cells but not in EBNA-3C knockout cells. Such differential response was not found in either EBNA-3A or EBNA-3B knockout and revertant pairs. Whilst vorinostat/bortezomib induced G2/M arrest in EBNA-3C knockout cells, it did not lead to G2/M arrest in EBNA-3C expressing cells. In vivo, vorinostat/bortezomib treatment resulted in enhanced suppression of the growth of EBNA-3C expressing but not in EBNA-3C knockout B cell xenografts in SCID mice. CONCLUSION: Combination of histone deacetylase and proteasome inhibitors induces enhanced killing of LCLs through suppression of the function of EBNA-3C protein and may represent a novel therapeutic regimen for PTLD.
DescriptionThis free journal suppl. entitled: Special Issue: Fifth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma Abstracts, 22 October 2015, Varese, Italy
Session - Lymphoma Translational Biology
Persistent Identifierhttp://hdl.handle.net/10722/222041
ISSN
2015 Impact Factor: 5.401
2015 SCImago Journal Rankings: 2.313

 

DC FieldValueLanguage
dc.contributor.authorYeung, PL-
dc.contributor.authorHui, KF-
dc.contributor.authorChiang, AKS-
dc.date.accessioned2015-12-21T05:53:30Z-
dc.date.available2015-12-21T05:53:30Z-
dc.date.issued2015-
dc.identifier.citationThe International Symposium on Childhood, Adolescent and. Young Adult Non-Hodgkin Lymphoma, Varese, Italy, 21-24 October 2015. In British Journal of Haematology, 2015, v. 171 suppl. S1, p. 38, abstract no. 65-
dc.identifier.issn0007-1048-
dc.identifier.urihttp://hdl.handle.net/10722/222041-
dc.descriptionThis free journal suppl. entitled: Special Issue: Fifth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma Abstracts, 22 October 2015, Varese, Italy-
dc.descriptionSession - Lymphoma Translational Biology-
dc.description.abstractBACKGROUND: Epstein-Barr virus (EBV) drives the development of post-transplant lymphoproliferative disorder (PTLD) via the concerted action of Epstein-Barr nuclear antigen (EBNA) proteins. We previously reported that combination of histone deacetylase inhibitor (HDACI) and proteasome inhibitor (PI) could synergistically induce apoptosis of lymphoblastoid cells (LCLS), an in-vitro cell model of PTLD, which express the EBNA-3A, -3B and -3C proteins. OBJECTIVES: We aim to investigate whether combination of HDACI and PI induces apoptosis of LCLs by suppressing the function of EBNA-3A, -3B or -3C protein. Design/Methods: Spontaneous LCLs and a panel of B cell lines harboring EBNA-3A, -3B or -3C knockout EBV genome and corresponding cell lines harboring the knockout virus together with the individual gene revertant were treated with combination of HDACI (vorinostat) and PI (bortezomib), followed by analyses of apoptosis and cell cycle. In-vivo testing of B cell xenografts in SCID mice was also performed. RESULTS: MTT assay showed that vorinostat/bortezomib induced enhanced cell death in EBNA-3C expressing cells but not in EBNA-3C knockout cells. Such differential response was not found in either EBNA-3A or EBNA-3B knockout and revertant pairs. Whilst vorinostat/bortezomib induced G2/M arrest in EBNA-3C knockout cells, it did not lead to G2/M arrest in EBNA-3C expressing cells. In vivo, vorinostat/bortezomib treatment resulted in enhanced suppression of the growth of EBNA-3C expressing but not in EBNA-3C knockout B cell xenografts in SCID mice. CONCLUSION: Combination of histone deacetylase and proteasome inhibitors induces enhanced killing of LCLs through suppression of the function of EBNA-3C protein and may represent a novel therapeutic regimen for PTLD.-
dc.languageeng-
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH-
dc.relation.ispartofBritish Journal of Haematology-
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.titleCombination of histone deacetylase and proteasome inhibitors induces enhanced killing of Epstein-Barr virus-positive lymphoblastoid cells through suppression of the function of EBNA-3c protein-
dc.typeConference_Paper-
dc.identifier.emailHui, KF: kfhui@hku.hk-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/bjh.13753-
dc.identifier.hkuros256359-
dc.identifier.volume171-
dc.identifier.issuesuppl. S1-
dc.identifier.spage38, abstract no. 65-
dc.identifier.epage38, abstract no. 65-
dc.publisher.placeUnited Kingdom-

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