{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:09:08Z","timestamp":1787857748734,"version":"build-2784847793"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the General Directorate of Academic Personnel Affairs, National Autonomous University of Mexico","award":["PAPIIT IN222023 and IA205324"],"award-info":[{"award-number":["PAPIIT IN222023 and IA205324"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chemoresistance is the leading cause of mortality in cancer patients. The poor clinical prognosis and limited therapeutic options for acute myeloid leukemia (AML) patients demand the development of new therapeutic strategies capable of overcoming chemoresistance and avoiding toxic side effects in normal cells. Sodium caseinate (SC), a derivative of casein protein found in milk, has demonstrated a dual role: it inhibits the proliferation of several murine AML cell lines while promoting the proliferation of normal hematopoietic cells. Furthermore, we previously showed that SC can modulate the expression of genes associated with chemoresistance in mouse cells. However, its biological effects on cytarabine-resistant human leukemia cells remain unclear. Here, we developed the HL60-CR50 subline, resistant to cytarabine, and investigated the effects of SC. We demonstrated that SC significantly reduced cell proliferation, decreased SIRT1 levels, increased acetylated p53, activated cleaved caspase-3, and enhanced apoptosis in cytarabine-resistant cells. These findings suggest that SC might have potential as a therapeutic adjuvant for AML, providing efficacy in chemoresistant cases compared with cytarabine treatment alone.<\/jats:p>","DOI":"10.3390\/molecules30244759","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T12:52:31Z","timestamp":1765543951000},"page":"4759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antileukemic Potential of Sodium Caseinate in Cytarabine-Resistant HL60-CR50 Human Leukemia Cells"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4876-0688","authenticated-orcid":false,"given":"Edelmiro","family":"Santiago-Osorio","sequence":"first","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-0240","authenticated-orcid":false,"given":"Daniel","family":"Romero-Trejo","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"},{"name":"Department of Biomedical Sciences, School of Medicine, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 56410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7799-866X","authenticated-orcid":false,"given":"V\u00edctor Manuel","family":"Mac\u00edas-Zaragoza","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"},{"name":"Department of Biomedical Sciences, School of Medicine, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 56410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5197-8862","authenticated-orcid":false,"given":"Katia Michell","family":"Rodr\u00edguez-Ter\u00e1n","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-3405","authenticated-orcid":false,"given":"V\u00edctor Manuel","family":"Mendoza-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Research Unit on Gerontology, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Sierra-Mondrag\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Biophysics, and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Romero-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Shira","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-1484","authenticated-orcid":false,"given":"David","family":"Hern\u00e1ndez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Research Unit on Gerontology, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-8287","authenticated-orcid":false,"given":"Itzen","family":"Agui\u00f1iga-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico"},{"name":"Department of Biomedical Sciences, School of Medicine, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City 56410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","first-page":"e33165","article-title":"Resistance Mechanism of Acute Myeloid Leukemia Cells Against Daunorubicin and Cytarabine: A Literature Review","volume":"14","author":"Arwanih","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ajh.24246","article-title":"Acute Myeloid Leukemia\u2014Major Progress over Four Decades and Glimpses into the Future","volume":"91","author":"Kantarjian","year":"2016","journal-title":"Am. 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