{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T16:17:07Z","timestamp":1768580227890,"version":"3.49.0"},"reference-count":81,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T00:00:00Z","timestamp":1459382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA160685"],"award-info":[{"award-number":["R01CA160685"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-12-214-01 \u2013 CCG"],"award-info":[{"award-number":["RSG-12-214-01 \u2013 CCG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14-1-0013"],"award-info":[{"award-number":["W81XWH-14-1-0013"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016056"],"award-info":[{"award-number":["P30 CA016056"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Development of therapeutic resistance is responsible for most prostate cancer (PCa) related mortality. Resistance has been attributed to an acquired or selected cancer stem cell phenotype. Here we report the histone deacetylase inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel (TXL)\u2010induced apoptosis in PCa cells and limit accumulation of cancer stem cells. TXL\u2010induced responses were modulated in the presence of TG with increased accumulation of cells at G1\u2010phase, rearrangement of the cytoskeleton, and changes in cytokine release. Cytoskeletal rearrangement was associated with modulation of the cytoplasmic and mitochondrial unfolded protein response leading to mitochondrial dysfunction and release of proapoptotic proteins from mitochondria. TXL in combination with APC or TG enhanced caspase activation. Importantly, TXL in combination with TG induced caspase activation and apoptosis in X\u2010ray resistant LNCaP cells. Increased release of transforming growth factor\u2010beta (TGF\u2010\u03b2) was observed while phosphorylated \u03b2\u2010catenin level was suppressed with TXL combination treatments. This was accompanied by a decrease in the CD44+CD133+ cancer stem cell\u2010like population, suggesting treatment affects cancer stem cell properties. Taken together, combination treatment with TXL and either APC or TG induces efficient apoptosis in both proliferating and cancer stem cells, suggesting this therapeutic combination may overcome drug resistance and recurrence in PCa.<\/jats:p>","DOI":"10.1016\/j.molonc.2016.03.007","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T03:31:40Z","timestamp":1459567900000},"page":"949-965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combination therapy induces unfolded protein response and\u00a0cytoskeletal rearrangement leading to mitochondrial apoptosis in prostate cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Sandeep","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay K.","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"O'Malley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Dubrovska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelu","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Goodrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhyan","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.06.017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.11.011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2284"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(95)00180-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.03.022"},{"key":"e_1_2_8_7_1","first-page":"415","article-title":"Thapsigargin induces mitochondrial dysfunction and apoptosis in the mastocytoma P815 cell line and in mouse thymocytes","volume":"3","author":"Beaver J.P.","year":"1996","journal-title":"Cell Death Differ"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.041"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8505"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-11-0180"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203834200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702777200"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207622200"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-552"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.06.004"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1924"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2018"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410690200"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3722"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(01)00404-9"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2015.02.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-053728"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920112802501962"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12475"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.4.1.10977"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.07.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.71.1.172"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.03.014"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.05.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.140120"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.202440"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-26"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1524"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml500315b"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737083"},{"key":"e_1_2_8_37_1","first-page":"275","article-title":"Bevacizumab plus weekly paclitaxel with or without carboplatin for previously-treated non-squamous non-small cell lung cancer","volume":"34","author":"Hata A.","year":"2014","journal-title":"Anticancer Res"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000835"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604242"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.01.018"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1875"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.090738"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.1.44"},{"key":"e_1_2_8_44_1","first-page":"2098","article-title":"Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer","volume":"9","author":"Kelly W.K.","year":"2003","journal-title":"Clin. Cancer Res. \u2013 Off. J. Am. Assoc. Cancer Res"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20053"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.9406"},{"key":"e_1_2_8_47_1","first-page":"1259","article-title":"Mifepristone-induced secretion of transforming growth factor beta1-induced apoptosis in prostate cancer cells","volume":"21","author":"Liang Y.","year":"2002","journal-title":"Int. J. Oncol"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1035"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.04.029"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010184"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.515"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1250704"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-04-0335"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-7-1"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2012.02.011"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63692-9"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.25231"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01819"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-126"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12019"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200512100"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2013.12.021"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3109\/09553002.2014.892227"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008797"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2012.04.001"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.03.034"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609353103"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21166"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-8-57"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11494"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22830"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049-3002-2-17"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.13"},{"key":"e_1_2_8_74_1","first-page":"2619","article-title":"Proliferation-dependent cytotoxicity of anticancer agents: a review","volume":"35","author":"Valeriote F.","year":"1975","journal-title":"Cancer Res"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc4016"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206334"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036545"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.405"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/np800662j"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.4.947"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.076752"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf445"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2016.03.007","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2016.03.007","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S157478911630014X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S157478911630014X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.molonc.2016.03.007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T15:13:31Z","timestamp":1717600411000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1016\/j.molonc.2016.03.007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,31]]},"references-count":81,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1016\/j.molonc.2016.03.007"],"URL":"https:\/\/doi.org\/10.1016\/j.molonc.2016.03.007","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,31]]},"assertion":[{"value":"2016-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}