{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:35:53Z","timestamp":1787009753500,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2002,6,7]],"date-time":"2002-06-07T00:00:00Z","timestamp":1023408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The T\u2010ALL cell lines CCRF\u2010CEM and Jurkat were studied for their sensitivity toward apoptosis induced by tetrocarcin\u2010A (TC\u2010A), an antibacterial and antitumor agent isolated from the actinomycete Micromonospora. This substance promoted cell death via a mitochondrial signaling pathway, that is, by activation of Bid and Bax, loss of the mitochondrial transmembrane potential, release of cytochrome c, and activation of effector caspases, even under conditions of Bcl\u20102 overexpression. Furthermore, sensitivity to TC\u2010A was not dependent on expression of wild\u2010type caspase\u20108. In contrast, this apoptotic pathway was inhibited markedly by pretreatment of cells with cycloheximide, an inhibitor of de novo protein synthesis. cDNA microarray chip analysis revealed that TC\u2010A induced a significant up\u2010regulation of members of the heat shock protein family known to be involved in the endoplasmic reticulum (ER)\u2010stressinduced apoptotic program. The activation of caspase\u201012, the central inducer caspase involved in ER\u2010stress by TC\u2010A treatment, is in concordance with this result. These results show that, in TALL cells, TC\u2010A induces an apoptotic machinery via mitochondrial and ER signaling, which is not inhibited by aberrant expression\/function of important regulators of death receptor\u2010 and druginduced apoptosis.<\/jats:p>","DOI":"10.1096\/fj.02-0020fje","type":"journal-article","created":{"date-parts":[[2002,9,30]],"date-time":"2002-09-30T13:43:21Z","timestamp":1033393401000},"page":"1295-1297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Stressful death of T\u2010ALL tumor cells following treatment with the antitumor agent Tetrocarcin\u2010A"],"prefix":"10.1096","volume":"16","author":[{"given":"Inge","family":"Tinhofer","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Cytology, Department of Hematology and Oncology University of Innsbruck  Innsbruck Austria"},{"name":"Tyrolean Cancer Research Institute University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Anether","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cytology, Department of Hematology and Oncology University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Senfter","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cytology, Department of Hematology and Oncology University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Pfaller","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Histology University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bernhard","sequence":"additional","affiliation":[{"name":"Tyrolean Cancer Research Institute University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsunobu","family":"Hara","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.  Shimotogari 1188, Nagaizumi \u2010cho Suntougun Shizuoka\u2010ken 411 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Greil","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cytology, Department of Hematology and Oncology University of Innsbruck  Innsbruck Austria"},{"name":"Tyrolean Cancer Research Institute University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,6,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-199911000-00008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004419900160"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.2.381"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35004029"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00008-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.5.729"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.3.929-935.2000"},{"key":"e_1_2_7_9_1","first-page":"271","article-title":"Regulation of bcl\u20102 gene expression in lymphoid cell lines containing normal #18 or t(14;18) chromosomes","volume":"4","author":"Reed J. C.","year":"1989","journal-title":"Oncogene Res"},{"key":"e_1_2_7_10_1","first-page":"1799","article-title":"Tumor suppressor p53 is a regulator of bcl\u20102 and bax gene expression in vitro and in vivo","volume":"9","author":"Miyashita T.","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_7_11_1","first-page":"9","article-title":"Antisense therapy of hematologic malignancies","volume":"36","author":"Cotter F. E.","year":"1999","journal-title":"Semin Hematol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.6.1675"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203824"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.5.1378"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/75007"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204750"},{"key":"e_1_2_7_17_1","first-page":"1033","volume-title":"3. Antitumor activity of tetrocarcin A","author":"Morimoto M.","year":"1982"},{"key":"e_1_2_7_18_1","first-page":"1229","article-title":"Tetrocarcin A inhibits mitochondrial functions of Bcl\u20102 and suppresses its anti\u2010apoptotic activity","volume":"60","author":"Nakashima T.","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/47513"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202339"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00420-4"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.5.1415.bloodjournal8451415"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(91)90198-O"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00669-8"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/2.4.329"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81589-5"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4644(20010101)80:1<53::AID-JCB60>3.0.CO;2-E"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400689"},{"key":"e_1_2_7_29_1","first-page":"887","article-title":"Cross\u2010talk between two cysteine protease families","volume":"150","author":"Nakagawa T.","year":"2000","journal-title":"Activation of caspase\u201012 by calpain in apoptosis. J Cell Biol"},{"key":"e_1_2_7_30_1","article-title":"Coupling endoplasmic reticulum stress to the cell death program","volume":"276","author":"Rao R. V.","year":"2001","journal-title":"mechanism of caspase activation. J Biol Chem"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81590-1"},{"key":"e_1_2_7_32_1","first-page":"623","article-title":"Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or bcl\u20102","volume":"2","author":"Wu G. S.","year":"1996","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(99)00124-0"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(99)00122-8"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1309\/491W-L1TN-UFQX-T61B"},{"key":"e_1_2_7_36_1","first-page":"1055","article-title":"Drug\u2010induced apoptosis in B\u2010cell chronic lymphocytic leukemia: relationship between p53 gene mutation and bcl\u20102\/bax proteins in drug resistance","volume":"12","author":"Thomas A.","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/ard.1994.4.71"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.624"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1131>3.0.CO;2-Y"},{"key":"e_1_2_7_40_1","first-page":"2492","article-title":"Eradication of human non\u2010Hodgkin's lymphoma in SCID mice by BCL\u20102 antisense oligonucleotides combined with low\u2010dose cyclophosphamide","volume":"6","author":"Klasa R. J.","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3929"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.5.891"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.9.2330"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055095"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5345.1966"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.2.554"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-574"},{"key":"e_1_2_7_48_1","first-page":"3331","article-title":"Drug\u2010induced apoptosis is associated with enhanced Fas (Apo\u20101\/CD95) ligand expression but occurs independently of Fas (Apo\u20101\/CD95) signaling in human T\u2010acute lymphatic leukemia cells","volume":"57","author":"Villunger A.","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_49_1","first-page":"203","article-title":"Drug\u2010induced apoptosis in lung cancer cells is not mediated by the Fas\/FasL (CD95\/APO1) signaling pathway","volume":"6","author":"Ferreira C. G.","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.3053.409a33_3053_3063"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090100233"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.10.1211"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/16729"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.14.1.459"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.27.120193.002253"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/35019501"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05605.x"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(2000)005<0443:HSPTFO>2.0.CO;2"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.02-0020fje","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.02-0020fje","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.02-0020fje","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:06:03Z","timestamp":1761667563000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.02-0020fje"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,6,7]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2002,8]]}},"alternative-id":["10.1096\/fj.02-0020fje"],"URL":"https:\/\/doi.org\/10.1096\/fj.02-0020fje","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,6,7]]},"assertion":[{"value":"2002-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-06-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}