{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:40:49Z","timestamp":1777948849579,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Colorectal cancer (CRC) remains one of the leading causes of cancer mortality, with a poor survival rate of less than 15%. Imatinib (IM) and Zebularine (ZEB) alone have shown potential effects in CRC treatment, but their combination has not been thoroughly studied. This study investigates the potential effects of IM and ZEB in colon cancer cells to provide a novel therapeutic agent for managing CRC. Cell growth inhibition, oxidative stress markers, and cell cycle progression were assessed in HCT\u2010116 cells treated with IM, ZEB, and their combinations. ZEB uptake levels were analyzed by LC\u2010MS\/MS, apoptosis was quantified by flow cytometry, and gene expression changes were analyzed by qPCR. The expression of metastatic markers, apoptotic regulators, and EGFR was assessed. Both IM and ZEB inhibited cell growth in a concentration\u2010dependent manner, and their combination showed synergistic effects. The combination significantly enhanced oxidative stress. The combination therapy increased apoptosis and necrosis. Furthermore, the combination induced significant S\u2010phase arrest in the cell cycle. The combination treatment reduced metastatic markers (MMP9, MMP2), and the apoptotic marker Caspase\u20109 was upregulated. Additionally, the Bcl\u20102 protein, a key regulator of apoptosis, was significantly downexpressed. Remarkably, the combination treatment showed significant inhibition in EGFR levels. Both IM and ZEB combination showed promise in the management of CRC by inducing oxidative stress, promoting apoptosis, and modulating critical genes involved in metastasis and apoptosis. Further investigation will be needed to verify their application in preclinical and clinical settings.<\/jats:p>","DOI":"10.1002\/jbt.70885","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T20:59:55Z","timestamp":1777841995000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zebularine Boosts Imatinib Efficacy in Cells of Colorectal Cancer via Wnt\u2010Survivin\u2010P\u2010Glycoprotein Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-2901","authenticated-orcid":false,"given":"Yasmin M.","family":"Attia","sequence":"first","affiliation":[{"name":"Cancer Biology Department, Pharmacology Unit, National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abeer","family":"Elkhoely","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Helwan University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma M.","family":"Abdelwahed","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Medical Biochemistry and Molecular Biology Unit. National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-8775","authenticated-orcid":false,"given":"Samia A.","family":"Shouman","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Pharmacology Unit, National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-0104","authenticated-orcid":false,"given":"Mervat M.","family":"Omran","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Pharmacology Unit, National Cancer Institute Cairo University Cairo Egypt"},{"name":"Department of Obstetrics and Gynecology University of Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jnma.2022.04.001","article-title":"Racial and Ethnic Disparities in Incidence and Mortality for the Five Most Common Gastrointestinal Cancers in the United States","volume":"114","author":"Bui A.","year":"2022","journal-title":"Journal of the National Medical Association"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","article-title":"Colorectal Cancer","volume":"394","author":"Dekker E.","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"e_1_2_9_4_1","first-page":"56","article-title":"Quality of Life in Non\u2010Metastasic Colorectal Cancer Patients in FOLFOX or XELOX Therapy","volume":"43","author":"S\u00e1nchez\u2010Gund\u00edn J.","year":"2019","journal-title":"Farmacia Hospitalaria"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0189-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.27188"},{"key":"e_1_2_9_7_1","unstructured":"NCCN. 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