{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:51:19Z","timestamp":1789419079712,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,18]],"date-time":"2013-02-18T00:00:00Z","timestamp":1361145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sodium valproate (VPA) has been recently identified as a selective class I histone deacetylase (HDAC) inhibitor and explored for its potential as an anti\u2010cancer agent. The anti\u2010cancer properties of VPA are generally attributed to its HDAC inhibitory activity indicating a clear overlap of these two actions, but the underlying mechanisms of its anti\u2010tumor effects are not clearly elucidated. The present study aimed to delineate the molecular mechanism of VPA in potentiating cytotoxic effects of anti\u2010cancer drugs with focus on inhibition of HDAC activity. Using human neuroblastoma cell lines, SK\u2010N\u2010MC, SH\u2010SY5Y, and SK\u2010N\u2010SH, we show that non\u2010toxic dose (2\u2009mM) of VPA enhanced staurosporine (STS)\u2010induced cell death as assessed by MTT assay, PARP cleavage, hypodiploidy, and caspase 3 activity. Mechanistically, the effect of VPA was mediated by down regulation of survivin, an anti\u2010apoptotic protein crucial in resistance to STS\u2010mediated cytotoxicity, through Akt pathway. Knock down of class I HDAC isoforms remarkably inhibited HDAC activity comparable with that of VPA but had no effect on STS\u2010induced apoptosis. Moreover, MS\u2010275, a structurally distinct class I HDAC inhibitor did not affect STS\u2010mediated apoptosis, nor decrease the levels of survivin and Akt. Valpromide (VPM), an amide analog of VPA that does not inhibit HDAC also potentiated cell death in NB cells associated with decreased survivin and Akt levels suggesting that HDAC inhibition might not be crucial for STS\u2010induced apoptosis. The study provides new information on the possible molecular mechanism of VPA in apoptosis that can be explored in combination therapy in cancer. J. Cell. Biochem. 114: 854\u2013863, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24422","type":"journal-article","created":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T17:17:48Z","timestamp":1351012668000},"page":"854-863","source":"Crossref","is-referenced-by-count":19,"title":["Sodium valproate potentiates staurosporine\u2010induced apoptosis in neuroblastoma cells via Akt\/survivin independently of HDAC inhibition"],"prefix":"10.1002","volume":"114","author":[{"given":"Reecha D.","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree C.","family":"Jagtap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mruthyunjaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh V.","family":"Shelke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Pujari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowry","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Shastry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2001.28839"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.4.623"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1476-5586(04)80051-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-5-71"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707608"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-70"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197801)41:1<56::AID-CNCR2820410110>3.0.CO;2-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2007.11.003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-383"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06714.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2478\/v10102-009-0019-x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.12.004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404496200"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(00)00013-9"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg816"},{"key":"e_1_2_6_18_1","first-page":"248","article-title":"The effects of the histone deacetylase inhibitor valproic acid on cell cycle, growth suppression and apoptosis in multiple myeloma","volume":"91","author":"Kaiser M","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2681"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2011.100"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070779"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.12.2607"},{"key":"e_1_2_6_23_1","first-page":"61","article-title":"Histone deacetylase inhibitors: Promising candidates for chemotherapeutic drugs","volume":"8","author":"Lindemann R","year":"2004","journal-title":"Gene Ther Mol Biol"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385524-4.00001-5"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35106079"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910143411601"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205353"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-007-9131-5"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-55"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01149.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2009.11.011"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-011-9431-7"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(68)80252-5"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.5.659"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920007780655397"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.6.1260"},{"key":"e_1_2_6_38_1","first-page":"347","article-title":"Actions of sodium valproate on the central nervous system","volume":"50","author":"Tunnicliff G","year":"1999","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.6.2.3578"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-1085-x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.03.165"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.24422","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.24422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T23:08:19Z","timestamp":1696892899000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.24422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,18]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/jcb.24422"],"URL":"https:\/\/doi.org\/10.1002\/jcb.24422","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,18]]}}}