{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:11Z","timestamp":1787029331580,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University, Riyadh, Saudi Arabia","doi-asserted-by":"publisher","award":["RSP2024R261"],"award-info":[{"award-number":["RSP2024R261"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Piano di Incentivi per la Ricerca di Ateneo 2020\u20132022, Linea di Intervento 2, \u201cIMYTRA\u201d","award":["RSP2024R261"],"award-info":[{"award-number":["RSP2024R261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib\/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib\/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.<\/jats:p>","DOI":"10.3390\/ph17070894","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6307-438X","authenticated-orcid":false,"given":"Mariarita","family":"Spampinato","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Zuppelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Dulcamare","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Longhitano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Sambataro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Santisi","sequence":"additional","affiliation":[{"name":"Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer M.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-0662","authenticated-orcid":false,"given":"Ignazio A.","family":"Barbagallo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-3962","authenticated-orcid":false,"given":"Nunzio","family":"Vicario","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-4696","authenticated-orcid":false,"given":"Rosalba","family":"Parenti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-4433","authenticated-orcid":false,"given":"Alessandra","family":"Romano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of General Surgery and Medical-Surgical Specialties, A.O.U. \u201cPoliclinico-Vittorio Emanuele\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-8890","authenticated-orcid":false,"given":"Giuseppe","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-2183","authenticated-orcid":false,"given":"Giovanni","family":"Li Volti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-6319","authenticated-orcid":false,"given":"Giuseppe A.","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of General Surgery and Medical-Surgical Specialties, A.O.U. \u201cPoliclinico-Vittorio Emanuele\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Unit, Ospedale Cannizzaro, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-7515","authenticated-orcid":false,"given":"Sebastiano","family":"Giallongo","sequence":"additional","affiliation":[{"name":"Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4405-2716","authenticated-orcid":false,"given":"Vittorio","family":"Del Fabro","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/jcmm.13326","article-title":"Monocytic myeloid-derived suppressor cells as prognostic factor in chronic myeloid leukaemia patients treated with dasatinib","volume":"22","author":"Giallongo","year":"2018","journal-title":"J. Cell Mol. 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