{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T07:54:38Z","timestamp":1764402878220},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Inhibition of histone deacetylases (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s) and subsequent hyperacetylation of histone proteins lead to altered gene expression associated with therapeutic drug effects, but also with teratogenicity. The only US Food and Drug Administration (<jats:styled-content style=\"fixed-case\">FDA)<\/jats:styled-content>\u2013approved antiepileptic drug that has been consistently shown to induce histone hyperacetylation is valproic acid. More recently, lacosamide was reported to interfere with histone modifications, but histone hyperacetylation was not demonstrated. In the current study we evaluated the effects of lacosamide on histone acetylation in\u00a0vitro. <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MB<\/jats:styled-content>\u2010231 (triple\u2010negative breast cancer) cells and human placental BeWo cells were exposed for 16\u00a0hours to 5\u201020\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">ml<\/jats:styled-content> (20\u201080\u00a0\u03bc<jats:sc>m<\/jats:sc>) lacosamide. Histone acetylation was evaluated by western blot analysis. We additionally measured <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>1 activity in the presence of lacosamide. At 5, 10, and 20\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">ml<\/jats:styled-content>, lacosamide enhanced histone acetylation in BeWo cells by 1.7\u2010fold (p<jats:italic>\u00a0<\/jats:italic>&gt;<jats:italic>\u00a0<\/jats:italic>0.05), 3.4\u2010fold (p<jats:italic>\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.05), and 3.0\u2010fold (p<jats:italic>\u00a0<\/jats:italic>&gt;<jats:italic>\u00a0<\/jats:italic>0.05), respectively. Histone H3 acetylation and total histones H3 and H4 levels were not significantly modified (p<jats:italic>\u00a0<\/jats:italic>&gt;<jats:italic>\u00a0<\/jats:italic>0.05). The magnitude of change in histone acetylation in <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MB<\/jats:styled-content>\u2010231 cells was smaller (p\u00a0&gt;\u00a00.05). In contrast to valproic acid, lacosamide did not inhibit <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>1. Our findings suggest that the effects of lacosamide on gene expression, and the related potential antitumor activity and teratogenicity, may differ from those of valproic acid.<\/jats:p>","DOI":"10.1002\/epi4.12269","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T16:25:43Z","timestamp":1537374343000},"page":"535-539","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Lacosamide at therapeutic concentrations induces histone hyperacetylation in\u00a0vitro"],"prefix":"10.1002","volume":"3","author":[{"given":"Avital","family":"Granit","sequence":"first","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"},{"name":"Sharett Institute of Oncology Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nino","family":"Tetro","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miri","family":"Shmuel","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamar","family":"Peretz","sequence":"additional","affiliation":[{"name":"Sharett Institute of Oncology Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Eyal","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.09.005"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2234-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2015.04.011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4360"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.02.012"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3425fje"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.00104.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14078"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.01.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12437"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.8595"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.1007\/s12035-017-0653-9","article-title":"CRMP2 phosphorylation drives glioblastoma cell proliferation","volume":"55","author":"Moutal A","year":"2018","journal-title":"Mol Neurobiol"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0546-9"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.04.009"},{"key":"e_1_2_7_18_1","unstructured":"Vimpat label. 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Revised 11\/2017 Accessed May 26 2018."},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.pjnns.2017.03.003","article-title":"Lacosamide during pregnancy and breastfeeding","volume":"51","author":"Lattanzi S","year":"2017","journal-title":"Neurol Neurochir Pol"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fepi4.12269","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T01:13:05Z","timestamp":1694740385000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,30]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/epi4.12269"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12269","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,30]]},"assertion":[{"value":"2018-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}