{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:05:58Z","timestamp":1784793958712,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Colorectal cancer remains one of the leading causes of cancer\u2010related mortality worldwide, highlighting the need for novel therapeutic agents with multitarget anticancer activity. Probucol is a phenolic compound with well\u2010established antioxidant and anti\u2010inflammatory properties; however, its effects on colorectal cancer cells have not been fully elucidated. The present study aimed to investigate the antitumor effects of probucol on SW480 human colorectal cancer cells and to explore the underlying molecular mechanisms focusing on cell cycle, apoptosis\u2010, and angiogenesis\u2010associated proteins. SW480 cells treated with probucol were subjected to MTT analysis. Cell cycle distribution and apoptosis were evaluated using cell cycle assay, Annexin V binding assay, and multicaspase activity assay. Apoptosis\u2010 and angiogenesis\u2010related protein expression was analyzed by western blot, matrix metalloproteinase\u20109 (MMP\u20109) mRNA expression was quantified by real\u2010time PCR. Probucol significantly reduced cell viability in a dose\u2010dependent manner and induced cell cycle arrest at the G0\/G1 phase. Treatment with probucol markedly increased early and late apoptotic cell populations and enhanced multicaspase activation. The upregulation of pro\u2010apoptotic Bax protein was accompanied by downregulation of antiapoptotic Bcl\u20102. In addition, probucol significantly suppressed the expression of angiogenesis\u2010associated proteins, including vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) and also decreased MMP\u20109 mRNA expression, indicating a potential antimetastatic effect. These findings demonstrate that probucol exerts significant anticancer effects on colorectal cancer cells by inhibiting cell proliferation, inducing apoptosis, and suppressing angiogenesis\u2010 and metastasis\u2010related molecular markers. Probucol may represent a promising candidate for further investigation as a potential multitarget agent in colorectal cancer.<\/jats:p>","DOI":"10.1111\/fcp.70104","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T06:20:42Z","timestamp":1782541242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Probucol Exerts Anticancer Effects on SW480 Human Colorectal Cancer Cells via Modulation of Apoptosis\u2010 and Angiogenesis\u2010Related Proteins"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-6293","authenticated-orcid":false,"given":"Ecem","family":"Kaya\u2010Sezginer","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Ankara University  Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-8946","authenticated-orcid":false,"given":"Filiz","family":"Bakar\u2010Ates","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Ankara University  Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5ra07380d"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202402479"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/639401"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1976206690"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.05.016"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.07.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.12807"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124021"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010024\u201000398\u2010w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42080-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/471590"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5tx00088b"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14191555"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.119301"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209789058048"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100008X259196"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e32832aee68"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060218"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2011.01.018"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349\u20107006.1999.tb00700.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1459057"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100773.2003.pto930602.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0008\u20106363(99)00400\u20109"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010051"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026104"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002176\u20100"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.9.2461.bloodjournal8592461"},{"issue":"7","key":"e_1_2_9_30_1","first-page":"1593","article-title":"Effects of Sophoridine on the Growth and Expressions of p53 and Vascular Endothelial Growth Factor of Transplanted Solid Tumor SW480 in Nude Mice","volume":"30","author":"Wang Q. 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