{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:47:54Z","timestamp":1790873274679,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,11,22]],"date-time":"2011-11-22T00:00:00Z","timestamp":1321920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>Epstein\u2013Barr virus (EBV), which infects B cells, T cells, and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, histone deacetylase (HDAC) inhibitors have been reported to have anticancer effects against various tumor cells. In the present study, we evaluated the killing effect of valproic acid (VPA), which acts as an HDAC inhibitor, on EBV\u2010positive and \u2010negative T and NK lymphoma cells. Treatment of multiple T and NK cell lines (SNT13, SNT16, Jurkat, SNK6, KAI3 and KHYG1) with 0.1\u20105 mM of VPA inhibited HDAC, increased acetylated histone levels and reduced cell viability. No significant differences were seen between EBV\u2010positive and \u2010negative cell lines. Although VPA induced apoptosis in some T and NK cell lines (SNT16, Jurkat and KHYG1) and cell cycle arrest, it did not induce lytic infection in EBV\u2010positive T or NK cell lines. Because the killing effect of VPA was modest (1 mM VPA reduced cell viability by between 22% and 56%), we tested the effects of the combination of 1 mM of VPA and 0.01 \u03bcM of the proteasome inhibitor bortezomib. The combined treated of cells with VPA and bortezomib had an additive killing effect. Finally, we administered VPA to peripheral blood mononuclear cells from three patients with EBV\u2010associated T or NK lymphoproliferative diseases. In these studies, VPA had a greater killing effect against EBV\u2010infected cells than uninfected cells, and the effect was increased when VPA was combined with bortezomib. These results indicate that VPA has antitumor effects on T and NK lymphoma cells and that VPA and bortezomib may have synergistic effects, irrespective of the presence of EBV. (<jats:italic>Cancer Sci<\/jats:italic> 2012; 103: 375\u2013381)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2011.02127.x","type":"journal-article","created":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T19:08:56Z","timestamp":1319224136000},"page":"375-381","source":"Crossref","is-referenced-by-count":23,"title":["Antitumor activities of valproic acid on Epstein\u2013Barr virus\u2010associated T and natural killer lymphoma cells"],"prefix":"10.1111","volume":"103","author":[{"given":"Seiko","family":"Iwata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Kamakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensei","family":"Gotoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010ichi","family":"Kawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,22]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008173430707"},{"key":"e_1_2_7_3_2","first-page":"278","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Quintanilla\u2010Martinez L","year":"2008"},{"key":"e_1_2_7_4_2","first-page":"2655","volume-title":"Fields Virology","author":"Rickinson AB","year":"2007"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2702"},{"key":"e_1_2_7_6_2","first-page":"2603","volume-title":"Fields Virology","author":"Kieff ED","year":"2007"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1110"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-143545"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303740200"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2133"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(01)00151-5"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0100"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1006"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24945"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25873"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04359.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00836.x"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830010206"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401769"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/294770a0"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.6.3900-3903.1995"},{"key":"e_1_2_7_22_2","first-page":"406","article-title":"Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia","volume":"24","author":"Robertson MJ","year":"1996","journal-title":"Exp Hematol"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604764"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.013482-0"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2007.08.012"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0166"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/605610"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/427239"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.2.280"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/367988"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp064"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.505"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0547"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.1398"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25584"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.04.001"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809090200"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-76-6-1409"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3569"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-345702"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-010-0614-9"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1349-7006.2011.02127.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1349-7006.2011.02127.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T12:26:32Z","timestamp":1737721592000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1349-7006.2011.02127.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,22]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1111\/j.1349-7006.2011.02127.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1349-7006.2011.02127.x","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,22]]}}}