{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:54:12Z","timestamp":1778781252432,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T00:00:00Z","timestamp":1406246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib is a principal therapeutic agent for targeting colorectal tumours. However, mono\u2010targeting by imatinib does not always achieve complete cancer eradication. Selenite, a well\u2010known chemopreventive agent, is commonly used in cancer patients. In this study, we aimed to explore whether selenite can modulate imatinib cytotoxicity in colorectal cancer cells. <jats:styled-content style=\"fixed-case\">HCT<\/jats:styled-content>116 cells were treated with different concentrations of imatinib and\/or selenite for 24, 48 and 72\u00a0hr. Imatinib\u2013selenite interaction was analysed using isobologram equation. As indicators of apoptosis, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation, caspase\u20103 activity, Bcl\u20102 expression were explored. Autophagic machinery was also checked by visualizing acidic vesicular organelles and measuring Beclin\u20101 expression. Furthermore, reactive oxygen and nitrogen species were also examined. This study demonstrated that selenite synergistically augmented imatinib cytotoxicity in <jats:styled-content style=\"fixed-case\">HCT<\/jats:styled-content>116 cells as demonstrated by combination and dose reduction indices. Supranutritional dose of selenite when combined with imatinib induced apoptotic machinery by decreasing Bcl\u20102 expression, increasing caspase\u20103 activity and subsequently fragmenting <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> and blunted cytoprotective autophagy by decreasing Beclin\u20101 expression and autophagosomes formation. Moreover, their combination induced cell cycle S\u2010phase block, increased total thiol content and reduced nitric oxide levels. In conclusion, selenite synergizes imatinib cytotoxicity through multi\u2010barrelled molecular targeting, providing a novel therapeutic approach for colorectal cancer.<\/jats:p>","DOI":"10.1111\/bcpt.12281","type":"journal-article","created":{"date-parts":[[2014,6,13]],"date-time":"2014-06-13T14:56:29Z","timestamp":1402671389000},"page":"37-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Modulation of Imatinib Cytotoxicity by Selenite in <scp>HCT<\/scp>116 Colorectal Cancer Cells"],"prefix":"10.1111","volume":"116","author":[{"given":"Amal Kamal","family":"Abdel\u2010Aziz","sequence":"first","affiliation":[{"name":"Pharmacology &amp; Toxicology Department Faculty of Pharmacy Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar Saad Eldeen","family":"Azab","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Toxicology Department Faculty of Pharmacy Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar Samir","family":"Youssef","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Department National Research Center Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abeer Mostafa","family":"El\u2010Sayed","sequence":"additional","affiliation":[{"name":"Tissue Culture &amp; Cytogenetics Unit Pathology Department National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebtehal","family":"El\u2010Demerdash","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Toxicology Department Faculty of Pharmacy Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia","family":"Shouman","sequence":"additional","affiliation":[{"name":"Cancer Biology Department National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2010.06.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441404"},{"key":"e_1_2_7_5_1","first-page":"4879","article-title":"The c\u2010kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy","volume":"62","author":"Attoub S","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812413106"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000248107"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21383"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209787582219"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.3.1070"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.103929"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130067"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25029"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2009.42.9.599"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2377"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.8.13430"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.2.1493"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02789164"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-006-9065-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635580802404188"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.13.1107"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-005-0046-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2000.0319"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-010-0595-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.1.181"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.01.026"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1385\/BTER:99:1-3:017"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209738"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/376037a0"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.10.014"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2009.07.012"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2239"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.07.003"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.09.040"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401777"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404606"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2012.45.3.194"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.06.007"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2011.12.010"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605904"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000038"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.08.201"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-2023"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2012.02.006"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203698"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e3283140c6f"},{"key":"e_1_2_7_49_1","first-page":"4965","article-title":"Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium","volume":"57","author":"Gallegos A","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0192"},{"key":"e_1_2_7_51_1","first-page":"163","article-title":"Multi\u2010target approaches in colon cancer chemoprevention based on systems biology of tumor cell\u2010signaling","volume":"2","author":"Guruswamy S","year":"2008","journal-title":"Gene Regul Syst Bio"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.12281","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.12281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T00:59:46Z","timestamp":1695517186000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.12281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,25]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1111\/bcpt.12281"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.12281","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,25]]},"assertion":[{"value":"2014-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}