{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:23:22Z","timestamp":1790922202641,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Among the phenolic acids tested on the K562 cell line, a model of chronic myeloid leukemia (CML), caffeic acid (CA) was biologically active on sensitive and imatinib (IM)-resistant cells at micro-molar concentration, either in terms of reduction of cell proliferation or triggering of apoptosis. The CA treatment provoked mitochondrial membrane depolarization, genomic DNA fragmentation and phosphatidylserine exposure, hallmarks of apoptosis. Cell cycle analysis following the treatment with comparable cytotoxic concentrations of IM or CA showed marked differences in the distribution profiles. The reduction of cell proliferation by CA administration was associated with increased expression of two cell cycle repressor genes, CDKN1A and CHES1, while IM at a cytotoxic concentration increased the CHES1 but not the CDKN1A expression. In addition, CA treatment affected the proliferation and triggered the apoptosis in IM-resistant cells. Taken together, these data suggested that CA induced the anti-proliferative effect and triggered apoptosis of CML cells by a different mechanism than IM. Finally, the combined administration of IM and CA at suboptimal concentrations evidenced a synergy of action in determining the anti-proliferative effect and triggering apoptosis. The ability of CA to potentiate the anti-leukemic effect of IM highlighted the nutraceutical potential of CA in CML.<\/jats:p>","DOI":"10.3390\/ijms22041644","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T14:07:19Z","timestamp":1612706839000},"page":"1644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Caffeic Acid Enhances the Anti-Leukemic Effect of Imatinib on Chronic Myeloid Leukemia Cells and Triggers Apoptosis in Cells Sensitive and Resistant to Imatinib"],"prefix":"10.3390","volume":"22","author":[{"given":"Giordana","family":"Feriotto","sequence":"first","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Tagliati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Giriolo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-3335","authenticated-orcid":false,"given":"Fabio","family":"Casciano","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-285X","authenticated-orcid":false,"given":"Claudio","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Beninati","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-5747","authenticated-orcid":false,"given":"Mahmud Tareq Hassan","family":"Khan","sequence":"additional","affiliation":[{"name":"Drug Discovery &amp; Design, AuraDynamics AS, 9012 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0029-2205","authenticated-orcid":false,"given":"Carlo","family":"Mischiati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.beha.2009.07.007","article-title":"Epidemiology of chronic myeloid leukaemia (CML)","volume":"22","author":"Rohrbacher","year":"2009","journal-title":"Best Pract. 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