{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:40:26Z","timestamp":1790707226934,"version":"4.1.0"},"reference-count":56,"publisher":"Spandidos Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7]]},"DOI":"10.3892\/ijo.2015.2996","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T08:36:41Z","timestamp":1431333401000},"page":"343-352","source":"Crossref","is-referenced-by-count":42,"title":["The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells"],"prefix":"10.3892","volume":"47","author":[{"given":"TOMAS","family":"GROH","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAN","family":"HRABETA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MOHAMMED ASHRAF","family":"KHALIL","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HELENA","family":"DOKTOROVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TOMAS","family":"ECKSCHLAGER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIE","family":"STIBOROVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2249","published-online":{"date-parts":[[2015,5,11]]},"reference":[{"key":"key20180107191106_b1-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrc1014","article-title":"Neuroblastoma: Biological insights into a clinical enigma","volume":"3","author":"Brodeur","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"key20180107191106_b2-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S1470-2045(03)01166-5","article-title":"Neuroblastoma: Biology and molecular and chromosomal pathology","volume":"4","author":"Schwab","year":"2003","journal-title":"Lancet Oncol"},{"key":"key20180107191106_b3-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(07)60983-0","article-title":"Neuroblastoma","volume":"369","author":"Maris","year":"2007","journal-title":"Lancet"},{"key":"key20180107191106_b4-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1002\/ijc.22401","article-title":"Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood","volume":"120","author":"Furchert","year":"2007","journal-title":"Int J Cancer"},{"key":"key20180107191106_b5-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"962","DOI":"10.4161\/epi.6.8.16516","article-title":"Neuroblastoma epigenetics: From candidate gene approaches to genome-wide screenings","volume":"6","author":"Decock","year":"2011","journal-title":"Epigenetics"},{"key":"key20180107191106_b6-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2174\/138920007780655397","article-title":"Histone deacetylase inhibitors: Molecular and biological activity as a premise to clinical application","volume":"8","author":"Santini","year":"2007","journal-title":"Curr Drug Metab"},{"key":"key20180107191106_b7-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/nbt.1685","article-title":"Epigenetic modifications and human disease","volume":"28","author":"Portela","year":"2010","journal-title":"Nat Biotechnol"},{"key":"key20180107191106_b8-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"key20180107191106_b9-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.gene.2005.09.010","article-title":"Acetylation and deacetylation of non-histone proteins","volume":"363","author":"Glozak","year":"2005","journal-title":"Gene"},{"key":"key20180107191106_b10-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.2174\/092986712802884286","article-title":"The synergistic effects of DNA-targeted chemotherapeutics and histone deacetylase inhibitors as therapeutic strategies for cancer treatment","volume":"19","author":"Stiborov\u00e1","year":"2012","journal-title":"Curr Med Chem"},{"key":"key20180107191106_b11-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/sj.bjc.6603851","article-title":"Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial","volume":"97","author":"Atmaca","year":"2007","journal-title":"Br J Cancer"},{"key":"key20180107191106_b12-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1158\/1078-0432.CCR-08-1930","article-title":"Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: Phase I\/II trial of valproic acid and epirubicin\/FEC","volume":"15","author":"Munster","year":"2009","journal-title":"Clin Cancer Res"},{"key":"key20180107191106_b13-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/sj.bjc.6604817","article-title":"A phase I\u2013II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma","volume":"100","author":"Rocca","year":"2009","journal-title":"Br J Cancer"},{"key":"key20180107191106_b14-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1158\/1078-0432.CCR-08-1579","article-title":"Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma","volume":"15","author":"Vandermeers","year":"2009","journal-title":"Clin Cancer Res"},{"key":"key20180107191106_b15-ijo-47-01-0343","first-page":"7291","article-title":"Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA","volume":"63","author":"Kim","year":"2003","journal-title":"Cancer Res"},{"key":"key20180107191106_b16-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.1158\/1078-0432.CCR-04-2088","article-title":"Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity","volume":"11","author":"Munshi","year":"2005","journal-title":"Clin Cancer Res"},{"key":"key20180107191106_b17-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1016\/j.ejca.2010.05.010","article-title":"Chromatin remodelling at the topoisomerase II-beta promoter is associated with enhanced sensitivity to etoposide in human neuroblastoma cell lines","volume":"46","author":"Das","year":"2010","journal-title":"Eur J Cancer"},{"issue":"Suppl 1","key":"key20180107191106_b18-ijo-47-01-0343","first-page":"101","article-title":"Anticancer agent ellipticine combined with histone deacetylase inhibitors, valproic acid and trichostatin A, is an effective DNA damage strategy in human neuroblastoma","volume":"32","author":"Poljakova","year":"2011","journal-title":"Neuro Endocrinol Lett"},{"key":"key20180107191106_b19-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3892\/or.2011.1577","article-title":"Valproic acid overcomes hypoxia-induced resistance to apoptosis","volume":"27","author":"Cipro","year":"2012","journal-title":"Oncol Rep"},{"issue":"Suppl 3","key":"key20180107191106_b20-ijo-47-01-0343","first-page":"S16","article-title":"Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells","volume":"33","author":"Groh","year":"2012","journal-title":"Neuro Endocrinol Lett"},{"key":"key20180107191106_b21-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"e76662","DOI":"10.1371\/journal.pone.0076662","article-title":"Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS One"},{"key":"key20180107191106_b22-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"161","DOI":"10.5507\/bp.2013.085","article-title":"Histone deacetylase inhibitors in cancer therapy. A review","volume":"158","author":"Hrabeta","year":"2014","journal-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub"},{"key":"key20180107191106_b23-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0027-5107(01)00141-5","article-title":"Mechanisms of resistance to cisplatin","volume":"478","author":"Kartalou","year":"2001","journal-title":"Mutat Res"},{"key":"key20180107191106_b24-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/bjc.1997.363","article-title":"Role of reactive oxygen species in cis-dichlorodi-ammineplatinum-induced cytotoxicity on bladder cancer cells","volume":"76","author":"Miyajima","year":"1997","journal-title":"Br J Cancer"},{"key":"key20180107191106_b25-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"8168","DOI":"10.1038\/sj.onc.1206979","article-title":"DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation","volume":"22","author":"Huang","year":"2003","journal-title":"Oncogene"},{"key":"key20180107191106_b26-ijo-47-01-0343","first-page":"120","article-title":"DNA damage as a basis for 4\u2032-demethy-lepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyranoside) (etoposide) cytotoxicity","volume":"43","author":"Wozniak","year":"1983","journal-title":"Cancer Res"},{"key":"key20180107191106_b27-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/S0959-8049(98)00228-7","article-title":"Etoposide: Four decades of development of a topoisomerase II inhibitor","volume":"34","author":"Hande","year":"1998","journal-title":"Eur J Cancer"},{"key":"key20180107191106_b28-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2174\/1568011054222364","article-title":"Etoposide, topoisomerase II and cancer","volume":"5","author":"Baldwin","year":"2005","journal-title":"Curr Med Chem Anticancer Agents"},{"key":"key20180107191106_b29-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.molonc.2012.09.003","article-title":"HDAC inhibitor-based therapies: Can we interpret the code?","volume":"6","author":"New","year":"2012","journal-title":"Mol Oncol"},{"key":"key20180107191106_b30-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"17174","DOI":"10.1016\/S0021-9258(17)44885-X","article-title":"Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A","volume":"265","author":"Yoshida","year":"1990","journal-title":"J Biol Chem"},{"key":"key20180107191106_b31-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.juro.2010.10.034","article-title":"The histone deacetylase inhibitor trichostatin A synergistically resensitizes a cisplatin resistant human bladder cancer cell line","volume":"185","author":"Yoon","year":"2011","journal-title":"J Urol"},{"key":"key20180107191106_b32-ijo-47-01-0343","first-page":"384","article-title":"The histone deacetylase inhibitor trichostatin A induces cell cycle arrest and apoptosis in colorectal cancer cells via p53-dependent and -independent pathways","volume":"28","author":"Meng","year":"2012","journal-title":"Oncol Rep"},{"key":"key20180107191106_b33-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.bcp.2009.01.021","article-title":"The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells","volume":"77","author":"Poljakov\u00e1","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"key20180107191106_b34-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.3892\/or.2014.2999","article-title":"Hypoxia-mediated histone acetylation and expression of N-myc transcription factor dictate aggressiveness of neuroblastoma cells","volume":"31","author":"Poljakov\u00e1","year":"2014","journal-title":"Oncol Rep"},{"key":"key20180107191106_b35-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1038\/nprot.2007.202","article-title":"Extraction, purification and analysis of histones","volume":"2","author":"Shechter","year":"2007","journal-title":"Nat Protoc"},{"key":"key20180107191106_b36-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J Biol Chem"},{"key":"key20180107191106_b37-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-61779-108-6_6","article-title":"The xCELLigence system for real-time and label-free monitoring of cell viability","volume":"740","author":"Ke","year":"2011","journal-title":"Methods Mol Biol"},{"key":"key20180107191106_b38-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1146\/annurev.biochem.68.1.383","article-title":"Mammalian caspases: Structure, activation, substrates, and functions during apoptosis","volume":"68","author":"Earnshaw","year":"1999","journal-title":"Annu Rev Biochem"},{"key":"key20180107191106_b39-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ"},{"key":"key20180107191106_b40-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1074\/jbc.M008363200","article-title":"Executioner caspase-3, \u22126, and \u22127 perform distinct, non-redundant roles during the demolition phase of apoptosis","volume":"276","author":"Slee","year":"2001","journal-title":"J Biol Chem"},{"key":"key20180107191106_b41-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1089\/adt.2006.4.597","article-title":"Dynamic and label-free cell-based assays using the real-time cell electronic sensing system","volume":"4","author":"Atienza","year":"2006","journal-title":"Assay Drug Dev Technol"},{"key":"key20180107191106_b42-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv Enzyme Regul"},{"key":"key20180107191106_b43-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol Rev"},{"key":"key20180107191106_b44-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.4161\/cc.10.18.17190","article-title":"Schedule-dependent synergy of histone deacetylase inhibitors with DNA damaging agents in small cell lung cancer","volume":"10","author":"Luchenko","year":"2011","journal-title":"Cell Cycle"},{"key":"key20180107191106_b45-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"key20180107191106_b46-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3892\/ijmm.2012.1167","article-title":"Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells","volume":"31","author":"Tu","year":"2013","journal-title":"Int J Mol Med"},{"key":"key20180107191106_b47-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"Phiel","year":"2001","journal-title":"J Biol Chem"},{"key":"key20180107191106_b48-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.4161\/cc.6.18.4682","article-title":"gamma-H2AX in bystander cells: Not just a radiation-triggered event, a cellular response to stress mediated by intercellular communication","volume":"6","author":"Sokolov","year":"2007","journal-title":"Cell Cycle"},{"key":"key20180107191106_b49-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"GammaH2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"key20180107191106_b50-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4161\/cc.9.2.10475","article-title":"The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks","volume":"9","author":"Nakamura","year":"2010","journal-title":"Cell Cycle"},{"key":"key20180107191106_b51-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1016\/j.febslet.2010.05.021","article-title":"Focus on histone variant H2AX: To be or not to be","volume":"584","author":"Yuan","year":"2010","journal-title":"FEBS Lett"},{"key":"key20180107191106_b52-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.leukres.2008.07.003","article-title":"Sodium butyrate enhances the cytotoxic effect of antineoplastic drugs in human lymphoblastic T-cells","volume":"33","author":"dos Santos","year":"2009","journal-title":"Leuk Res"},{"key":"key20180107191106_b53-ijo-47-01-0343","first-page":"121","article-title":"The histone deacetylase inhibitor sodium butyrate induces DNA topoisomerase II alpha expression and confers hypersensitivity to etoposide in human leukemic cell lines","volume":"1","author":"Kurz","year":"2001","journal-title":"Mol Cancer Ther"},{"key":"key20180107191106_b54-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1158\/1535-7163.MCT-09-0254","article-title":"Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis","volume":"8","author":"Bruzzese","year":"2009","journal-title":"Mol Cancer Ther"},{"key":"key20180107191106_b55-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3109\/10715762.2011.591391","article-title":"Cisplatin induces production of reactive oxygen species via NADPH oxidase activation in human prostate cancer cells","volume":"45","author":"Itoh","year":"2011","journal-title":"Free Radic Res"},{"key":"key20180107191106_b56-ijo-47-01-0343","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1158\/1078-0432.CCR-06-1751","article-title":"Abrogation of MAPK and Akt signaling by AEE788 synergistically potentiates histone deacetylase inhibitor-induced apoptosis through reactive oxygen species generation","volume":"13","author":"Yu","year":"2007","journal-title":"Clin Cancer Res"}],"container-title":["International Journal of Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spandidos-publications.com\/10.3892\/ijo.2015.2996\/download","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T19:50:50Z","timestamp":1651953050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.spandidos-publications.com\/10.3892\/ijo.2015.2996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,11]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,5,11]]},"published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.3892\/ijo.2015.2996"],"URL":"https:\/\/doi.org\/10.3892\/ijo.2015.2996","relation":{},"ISSN":["1019-6439","1791-2423"],"issn-type":[{"value":"1019-6439","type":"print"},{"value":"1791-2423","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,11]]}}}