{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:00:43Z","timestamp":1784912443029,"version":"3.55.0"},"reference-count":26,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med Princ Pract"],"abstract":"<jats:p>Objective: This research aimed to assess thymoquinone (TQ)\u2019s potential to demethylate and re-express the suppressor of cytokine signaling-3 (SOCS-3) in the chronic myeloid leukemia (CML) mice model. Subject and Methods: A nude mouse model of CML was established, and the apoptotic influence of TQ was identified. TQ\u2019s impact on the target gene expressions was examined using real-time quantitative PCR (RT-qPCR), and SOCS-3 methylation was assessed by pyrosequencing. TQ\u2019s effects on the extracellular signal-regulated kinase 1 (ERK1) and ERK2 phosphorylation were assessed using Jess Simple Western analysis. Molecular docking of TQ\u2019s interaction with the anti-apoptotic proteins was assessed. Results: TQ exerted a marked hypomethylating influence on SOCS-3 and reduced ERK1\/2 phosphorylation level in K562-xenograft tumors. TQ also significantly upregulated the apoptosis-related cysteine peptidase (Caspase-3), BCL-2-interacting mediator of cell death (Bim), p53-upregulated modulator of apoptosis (PUMA), and other apoptotic genes and downregulated B-cell lymphoma 2 (BCL-2), BCL2-like 2 (BCL-w), survivin, and X-linked inhibitor of apoptosis (XIAP) in K562 cells. TQ also exhibited marked inhibitory properties on BCL-2-related gene expressed in fetal liver (BFL-1), B-cell lymphoma-extra large (BCL-xL), myeloid cell leukemia-1 (MCL-1), and BCL-2 proteins. This led to growth inhibition and apoptosis of the K562-tumour xenograft. Conclusion: These results indicate that TQ enhances CML cells\u2019 apoptosis by hypomethylating and re-expressing SOCS-3, inhibiting ERK1\/2, and modulating the apoptosis-regulator gene expression and by showing consistent interaction with most of the anti-apoptotic proteins, highlighting its potential as a scaffold for designing novel inhibitors to combat CML cells.<\/jats:p>","DOI":"10.1159\/000552709","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T16:00:37Z","timestamp":1779552037000},"page":"1-18","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Reactivation of SOCS-3 and Inhibition of ERK1\/2 Underlie Thymoquinone-Induced Apoptosis in a Chronic Myeloid Leukemia Xenograft Model"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-5679","authenticated-orcid":false,"given":"Futoon Abedrabbu","family":"Al-Rawashde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moath","family":"Alqaraleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diya","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-001X","authenticated-orcid":false,"given":"Abdullrahman","family":"Elsayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Anis Ashiela mohd","family":"Amiludin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fouad Saleih Resq","family":"Al-Suede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Ali Nagi","family":"Al-Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16060884"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/ph15091123"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1613"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3390\/ph14121287"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.21608\/resoncol.2022.114548.1159"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.02.006"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.855307"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051287"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0255-7"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2021.22.12.3959"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2016.17.2.703"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cogc.2014.12.004"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2020.100747"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1590\/s1984-82502011000400025"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404198"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3892\/ijo_00000464"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3687700"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-868752"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.2147\/CE.S42568"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031633"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16431"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3973"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23580"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2703-4"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3390\/nu14102120"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2011.608663"}],"container-title":["Medical Principles and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000552709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:01:57Z","timestamp":1784908917000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000552709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":26,"URL":"https:\/\/doi.org\/10.1159\/000552709","archive":["Portico"],"relation":{},"ISSN":["1011-7571","1423-0151"],"issn-type":[{"value":"1011-7571","type":"print"},{"value":"1423-0151","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]}}}