{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:05:45Z","timestamp":1761217545809},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T00:00:00Z","timestamp":1344470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The E2F1 gene well known is its pivotal role in regulating the entry from G1 to S phase, while the salvage antitumoral pathway which implicates it, especially in the absence of p53, is not fully characterized. We therefore attempted to identify the up\u2010 and down\u2010stream events involved in the activation of the E2F1\u2010dependent pro\u2010apoptotic pathway. For this purpose, a amonafide analogue, 7\u2010d (2\u2010(3\u2010(2\u2010(Dimethylamino)ethylamino)propyl)\u20106\u2010(dodecylamino)\u20101<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>de<\/jats:italic>]isoquinoline\u20101,3(2<jats:italic>H<\/jats:italic>)\u2010dione) was screened, which exhibited high antitumor activity against p53\u2010deficient human Chronic Myelogenous Leukemia (CML) K562 cells. Analysis of flow cytometry and western blots of K562 cells treated with 7\u2010d revealed an appreciable G2\/M cycle arrest and apoptosis in a dose and time\u2010dependent manner via p53\u2010independent pathway. A striking increase in \u201cComet tail\u201d formation and \u03b3\u2010H2AX expression showed that DNA double strand breaks (DSB) were caused by 7\u2010d treatment. ATM\/ATR signaling was reported to connect E2F1 induction with apoptosis in response to DNA damage. Indeed, 7\u2010d\u2010induced G2\/M arrest and apoptosis were antagonized by ATM\/ATR signaling inhibitor, Caffeine, which suggested that ATM\/ATR signaling was activated by 7\u2010d treatment. Furthermore, the increased expression of E2F1, p73, and Apaf\u20101 and p73 dissociation from HDM2 was induced by 7\u2010d treatment, however, knockout of E2F1 expression reversed p73, Apaf\u20101, and p21<jats:sup>Cip1\/WAF1<\/jats:sup> expression, reactivated cell cycle progression, and inhibited 7\u2010d\u2010induced apoptosis. Altogether our results for the first time indicate that 7\u2010d mediates its growth inhibitory effects on CML p53\u2010deficient cells via the activation of an E2F1\u2010dependent mitochondrial and cell cycle checkpoint signaling pathway which subsequently targets p73, Apaf\u20101, and p21<jats:sup>Cip1\/WAF1<\/jats:sup>. J. Cell. Biochem. 113: 3165\u20133177, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24194","type":"journal-article","created":{"date-parts":[[2012,5,16]],"date-time":"2012-05-16T17:12:28Z","timestamp":1337188348000},"page":"3165-3177","source":"Crossref","is-referenced-by-count":8,"title":["E2F1\u2010dependent pathways are involved in amonafide analogue 7\u2010d\u2010induced DNA damage, G2\/M arrest, and apoptosis in p53\u2010deficient K562 cells"],"prefix":"10.1002","volume":"113","author":[{"given":"Yiquan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhong","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10158"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.5.3704"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.197"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100025u"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.08.019"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/157489210789702172"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0222-0"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6293"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-685"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200805200"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/b912685f"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.3.178"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03270-2"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2718"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00834"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.08.005"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312866200"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e3282f00e17"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709787846659"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-006-0012-y"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2005.70.002"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.06.026"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0553"},{"key":"e_1_2_5_25_1","first-page":"305","article-title":"Gamma\u2010H2AX \u2010 a novel biomarker for DNA double\u2010strand breaks","volume":"22","author":"Kuo LJ","year":"2008","journal-title":"In Vivo"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.029"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.09.013"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.034"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210707"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(93)90161-D"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00813-9"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9403-9"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-10-0341"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220903431069"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081160"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2007.03.001"},{"key":"e_1_2_5_37_1","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1128\/MCB.19.5.3257","article-title":"MDM2 suppresses p73 function without promoting p73 degradation","volume":"19","author":"Lu H","year":"1999","journal-title":"Mol Cell Biol"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789909576"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.5"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81400-2"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2004.06.015"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152008783497019"},{"key":"e_1_2_5_43_1","first-page":"4375","article-title":"Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine","volume":"59","author":"Sarkaria JN","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_5_44_1","first-page":"825","article-title":"Alteration of the MDM2\u2010p73\u2010P14ARF pathway related to tumour progression during urinary bladder carcinogenesis","volume":"14","author":"Schlott T","year":"2004","journal-title":"Int J Mol Med"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.02.002"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2007.08.010"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-009-0400-2"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.10.050"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051072"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467210902020149"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.06.004"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.24194","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.24194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:30:12Z","timestamp":1697293812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.24194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,9]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1002\/jcb.24194"],"URL":"https:\/\/doi.org\/10.1002\/jcb.24194","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,9]]}}}