{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:32:22Z","timestamp":1785843142934,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti\u2010AML activity of bortezomib (BTZ), emphasizing its anti\u2010LSC potential, using KG\u20101a cells, an AML cell line with stem\u2010like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem\u2010like features of KG\u20101a cells, as observed by the reduction in CD34\u2010 and CD123\u2010positive cells. A reduction in NF\u2010\u03baB p65 nuclear staining was observed in BTZ\u2010treated KG\u20101a cells, in addition to upregulation of the NF\u2010\u03baB inhibitor gene <jats:italic>NF\u039aBIB<\/jats:italic>. BTZ\u2010induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase\u20103 and cleaved PARP\u2010(Asp 214) level in KG\u20101a cells. Furthermore, BTZ\u2010induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z\u2010VAD\u2010(OMe)\u2010FMK, indicating that BTZ induces caspase\u2010mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG\u20101a cells, and BTZ\u2010induced apoptosis was partially prevented by pretreatment with the antioxidant <jats:italic>N<\/jats:italic>\u2010acetylcysteine, indicating that BTZ induces oxidative stress\u2010mediated apoptosis in KG\u20101a cells. At a dosage of 0.1\u2009mg\/kg every other day for 2\u2009weeks, BTZ significantly reduced the percentage of hCD45\u2010positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG\u20101a cells with tolerable toxicity. Taken together, these data indicate that the anti\u2010LSC potential of BTZ appears to be an important strategy for AML treatment.<\/jats:p>","DOI":"10.1111\/jcmm.18333","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T14:51:51Z","timestamp":1713883911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bortezomib suppresses acute myelogenous leukaemia stem\u2010like <scp>KG<\/scp>\u20101a cells via <scp>NF\u2010\u03baB<\/scp> inhibition and the induction of oxidative stress"],"prefix":"10.1111","volume":"28","author":[{"given":"Rafaela G. A.","family":"Costa","sequence":"first","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiara de S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina B. da C.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suellen L. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid R. S. B.","family":"Dias","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-2992","authenticated-orcid":false,"given":"Milena B. P.","family":"Soares","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"},{"name":"SENAI Institute for Innovation in Advanced Health Systems SENAI CIMATEC  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"de Faro\u00a0Valverde","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-2985","authenticated-orcid":false,"given":"Clarissa Araujo","family":"Gurgel\u00a0Rocha","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"},{"name":"Department of Propaedeutics, Faculty of Dentistry Federal University of Bahia (UFBA)  Salvador Bahia Brazil"},{"name":"Center for Biotechnology and Cell Therapy D'Or Institute for Research and Education (IDOR)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-334X","authenticated-orcid":false,"given":"Rosane Borges","family":"Dias","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"},{"name":"Department of Propaedeutics, Faculty of Dentistry Federal University of Bahia (UFBA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2063","authenticated-orcid":false,"given":"Daniel P.","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute Oswaldo Cruz Foundation (IGM\u2010FIOCRUZ\/BA)  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00425-3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00108-3"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280801"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33458"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280800"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2021.103277"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102692"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13040695"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02678"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lrr.2023.100374"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2013.02.002"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16377"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.12.017"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90396-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(91)90198-o"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0320(19970501)28:1<74::aid-cyto9>3.0.co;2-h"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.06.003"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2014.04.001"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001742"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2021.1927021"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20008"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-1010"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.206"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018023689"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.220962"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-110171"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.03.008"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-3018"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.222"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.18333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T04:43:27Z","timestamp":1714193007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.18333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/jcmm.18333"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.18333","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18333"}}