{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:08:43Z","timestamp":1787004523485,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:p>The anthracycline antibiotic idarubicin (IDA) induces double\u2010stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells. It is unclear whether the generation of ROS is associated with the apoptotic process. Using the T\u2010lymphoblastic leukaemic CEM cell line, we found that IDA\u2010induced DNA breaks were correlated with final cell death. The reduction in mitochondrial membrane potential (\u0394\u03a8m) and the generation of ROS occurred simultaneously with IDA\u2010induced activation of caspase\u20109 and caspase\u20103. Inhibition of caspases by a pan\u2010caspase inhibitor, benzyloxycarbonyl\u2010Val\u2010Ala\u2010Asp\u2010fluoromethyl ketone (Z\u2010VAD\u2010fmk) completely blocked IDA\u2010induced reduction of \u0394\u03a8m, apoptosis and final cell death. Interestingly, ROS generation was significantly enhanced by Z\u2010VAD\u2010fmk. ROS generation was neither caspase dependent nor part of the apoptotic process. IDA\u2010mediated reduction in \u0394\u03a8m is caspase dependent and is not a consequence of the generation of ROS. These results indicate that IDA\u2010induced generation of ROS and apoptosis are separate events. Inhibition of caspases facilitates IDA\u2010mediated generation of ROS.<\/jats:p>","DOI":"10.1046\/j.1365-2141.2001.03216.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T01:40:31Z","timestamp":1047346831000},"page":"817-825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Generation of reactive oxygen species is not involved in idarubicin\u2010induced apoptosis in human leukaemic cells"],"prefix":"10.1111","volume":"115","author":[{"given":"Feng\u2010Ting","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Kelsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian C.","family":"Newland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0300-483x(99)00041-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401803"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1182\/blood.V79.12.3267.3267","article-title":"Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug\u2010resistant leukemia cells","volume":"79","author":"Berman E.","year":"1992","journal-title":"Blood"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1124\/mol.51.6.1053","article-title":"Relationship between lethal effects and topoisomerase II\u2010mediated double\u2010stranded DNA breaks produced by anthracyclines with different sequence specificity","volume":"51","author":"Binaschi M.","year":"1997","journal-title":"Molecular Pharmacology"},{"key":"e_1_2_6_6_1","first-page":"365","article-title":"Comparative evaluation of the intracellular accumulation and DNA binding of idarubicin and daunorubicin in sensitive and multidrug\u2010resistant human leukemia K562 cells","volume":"16","author":"Bogush T.","year":"1996","journal-title":"Anticancer Research"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.1.37"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3410233"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400793"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4924"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-2952(98)00307-4"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050752"},{"key":"e_1_2_6_13_1","first-page":"25","article-title":"Introcellular pharmacokinetics of anthracyclines in human leukemia cells: correlation of DNA binding with apoptotic cell death","volume":"36","author":"Gieseler F.","year":"1998","journal-title":"International Journal of Clinical Pharmacology and Therapeutics"},{"key":"e_1_2_6_14_1","first-page":"2978","article-title":"Resistance to adriamycin: relationship to cytotoxicity of drug uptake and DNA single\u2010 and double\u2010strand breakage in cloned cell lines of adriamycin\u2010sensitive and \u2010resistant P388 leukemia","volume":"46","author":"Goldenberg G.J.","year":"1986","journal-title":"Cancer Research"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1182\/blood.V87.6.2401.bloodjournal8762401","article-title":"Increased activity and sensitivity of mitochondrial respiratory enzymes to TNF\u03b1\u2010induced inhibition is associated with increased cytotoxicity in drug\u2010resistant leukemic cell lines","volume":"87","author":"Jia L.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.2683085.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.7.2353"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1999.01771.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.2.414"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204628"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4680(00)00053-5"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.22.040182.001045"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4838"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000027205"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1182\/blood.V90.11.4578","article-title":"Modulation of idarubicin\u2010induced apoptosis in human acute myeloid leukemia blasts by all\u2010trans retinoic acid, 1,25 (OH)2 vitamin D3, and granulocyte\u2010macrophage colony\u2010stimulating factor","volume":"90","author":"Ketley N.J.","year":"1997","journal-title":"Blood"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0697-614"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)02188-4"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3420481"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(99)00069-1"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.3.257"},{"key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1182\/blood.V96.1.307","article-title":"Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis","volume":"96","author":"Shacter E.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(90)90155-C"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6093249"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.367"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2141.2001.03216.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2141.2001.03216.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2141.2001.03216.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T07:29:47Z","timestamp":1697441387000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2141.2001.03216.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,12]]}},"alternative-id":["10.1046\/j.1365-2141.2001.03216.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2141.2001.03216.x","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,12]]},"assertion":[{"value":"2001-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}