{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:51:41Z","timestamp":1789275101850,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,5]],"date-time":"2018-08-05T00:00:00Z","timestamp":1533427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Bebidas para la Salud y Bienestar"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tyrosine kinase inhibitors (<jats:styled-content style=\"fixed-case\">TKI<\/jats:styled-content>) have become a first\u2010line treatment for chronic myeloid leuakemia (<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">TKI<\/jats:styled-content>s efficiently target bulk <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> cells; however, they are unable to eliminate the leukaemic stem cell (<jats:styled-content style=\"fixed-case\">LSC<\/jats:styled-content>) population that causes resistance and relapse in <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> patients. In this study, we assessed the effects of parthenolide (<jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content>) and dimethyl amino parthenolide (<jats:styled-content style=\"fixed-case\">DMAPT<\/jats:styled-content>), two potent inhibitors of <jats:styled-content style=\"fixed-case\">LSC<\/jats:styled-content>s in acute myeloid leukaemia (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>), on <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> bulk and <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> primitive (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34<jats:sup>+<\/jats:sup>lin<jats:sup>\u2212<\/jats:sup>) cells. We found that both agents induced cell death in <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>, while having little effect on the equivalent normal hematopoietic cells. <jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DMAPT<\/jats:styled-content> caused an increase in reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) levels and inhibited <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation. <jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DMAPT<\/jats:styled-content> inhibited cell proliferation and induced cell cycle arrest in G<jats:sub>0<\/jats:sub> and G<jats:sub>2<\/jats:sub> phases. Furthermore, we found cell cycle inhibition to correlate with down\u2010regulation of cyclin D1 and cyclin A. In summary, our study shows that <jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DMAPT<\/jats:styled-content> have a strong inhibitory effect on <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> cells. Given that cell cycle arrest was not dependent on <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> induction, we speculate that this effect could be a direct consequence of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB inhibition and if this mechanism was to be evaded, <jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DMAPT<\/jats:styled-content> induced cell death would be potentiated.<\/jats:p>","DOI":"10.1111\/jcmm.13755","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T07:54:03Z","timestamp":1533628443000},"page":"4899-4912","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Parthenolide and <scp>DMAPT<\/scp> induce cell death in primitive <scp>CML<\/scp> cells through reactive oxygen 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