{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:27:07Z","timestamp":1790908027930,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,11,27]],"date-time":"2010-11-27T00:00:00Z","timestamp":1290816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA), constitute a novel class of anticancer agents that cause an increase in acetylated histones and thus restore the expression of dormant tumor\u2010suppressor and other genes related to cell differentiation, cell\u2010cycle arrest or apoptosis of tumor cells. The Ras inhibitor farnesylthiosalicylic acid (FTS, salirasib) attenuates cancer cell proliferation <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> and, under certain circumstances, induces cell death. FTS by itself does not induce differentiation or complete growth arrest. The abovementioned activity of VPA as a differentiation agent suggested that it might be worth investigating its possible therapeutic potential in synergistic combination with FTS. Here, we examined whether the combined application of VPA and FTS could synergistically inhibit the proliferation of cancer cells that express oncogenic K\u2010Ras (A549 nonsmall\u2010cell lung carcinoma cells), DLD1 (colon carcinoma cells) or chronically active wild\u2010type K\u2010Ras and constitutively active B\u2010Raf (ARO, thyroid carcinoma cells). The results showed that combined treatment with VPA and FTS synergistically reduces proliferation in all of these cancer cell lines by downregulating Ras and blocking the expression of Survivin and Aurora A. These alterations, which were most pronounced following the combined treatment, led to a mitotic crisis, as reflected by mislocalization of the chromosomal passenger complex. Our findings thus demonstrate that combination therapy with VPA and FTS might offer a promising therapeutic approach to the treatment of epithelial tumors.<\/jats:p>","DOI":"10.1002\/ijc.25367","type":"journal-article","created":{"date-parts":[[2010,4,5]],"date-time":"2010-04-05T14:53:51Z","timestamp":1270479231000},"page":"691-701","source":"Crossref","is-referenced-by-count":36,"title":["Downregulation of survivin and aurora A by histone deacetylase and RAS inhibitors: A new drug combination for cancer therapy"],"prefix":"10.1002","volume":"128","author":[{"given":"Anat","family":"Biran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brownstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit","family":"Haklai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Kloog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,11,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-007-9131-5"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920007780655397"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.14.12.1497"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802608784911581"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6554-5_13"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210620"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.2174\/138161207782360528","article-title":"Valproic acid as anti\u2010cancer drug","volume":"13","author":"Michaelis M","year":"2007","journal-title":"Curr Pharm Des"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.10017"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22891"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-0799"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01242.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21725"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0248-8663(96)81248-3"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-144790"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2005.11.002"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.10.001"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/07357900802087275"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/157489208783478702"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(00)01789-5"},{"key":"e_1_2_6_21_2","first-page":"555","article-title":"The Ras inhibitor S\u2010trans,trans\u2010farnesylthiosalicylic acid chemosensitizes human tumor cells without causing resistance","volume":"8","author":"Gana\u2010Weisz M","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202602"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.05.007"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-007-0451-6"},{"key":"e_1_2_6_25_2","first-page":"31","article-title":"Suppression of lung cancer tumor growth in a nude mouse model by the Ras inhibitor salirasib (farnesylthiosalicylic acid)","volume":"31","author":"Zundelevich A","year":"2007","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401334"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-009-2210-1"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.09.048"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.20533"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0193"},{"key":"e_1_2_6_31_2","first-page":"10","article-title":"[Role of survivin in mitosis]","volume":"53","author":"Wolanin K","year":"2007","journal-title":"Postepy Biochem"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20082410828"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2257"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-004-0307-3"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.7.9.6415"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2008.07.003"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4287"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00945-4"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.3.5381"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1247\/csf.26.653"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2008.004"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06340.x"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-12-1178"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.11.050"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302129"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21735"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl801"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04655"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536759100"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-04-0304"},{"key":"e_1_2_6_51_2","first-page":"1125","article-title":"Interactive effects of histone deacetylase inhibitors and TRAIL on apoptosis in human leukemia cells: involvement of both death receptor and mitochondrial pathways","volume":"16","author":"Shankar S","year":"2005","journal-title":"Int J Mol Med"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01186-4"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.08.025"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.006"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07185"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157425"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.25367","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.25367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T07:21:11Z","timestamp":1697527271000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.25367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,27]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1002\/ijc.25367"],"URL":"https:\/\/doi.org\/10.1002\/ijc.25367","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,27]]}}}