{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:21:02Z","timestamp":1787772062208,"version":"build-2784847793"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although 5-fluorouracil (5-FU) is a standard chemotherapeutic agent for colorectal cancer (CRC), its efficacy is often limited by chemoresistance. Irisin, an exercise-induced myokine, has demonstrated anticancer potential; however, its role in CRC remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Human HT-29 CRC cells were treated for 12 h with irisin (2, 20, and 200 ng\/mL) alone or combined with 5-FU (50 \u03bcM). Cell cycle progression and apoptosis were assessed by flow cytometry. Expression of cell cycle regulators (CCND1, CCND3, p21, and p27), apoptotic markers (BCL2, Bcl-2-associated X protein, cytochrome c, caspase-8, caspase-9, and caspase-3), and metabolic mediators (protein kinase B [Akt], mammalian target of rapamycin [mTOR], adenosine monophosphate-activated protein kinase [AMPK], and phosphatase and tensin homolog [PTEN]) was analyzed by quantitative reverse transcription-polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>While 5-FU induced G0\/G1 arrest with p21\/p27 upregulation, irisin alone or in combination exerted minimal additional effects on cell cycle progression. In contrast, high-dose irisin (200 ng\/mL) significantly increased apoptotic cell fractions and upregulated caspase-8 and caspase-3 without significant alteration of mitochondrial apoptotic gene expression. Combination treatment further enhanced apoptosis. Co-treatment also increased AMPK and PTEN mRNA levels while reducing Akt and mTOR mRNA levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Under the experimental conditions used, irisin potentiated 5-FU cytotoxicity in HT-29 CRC cells primarily through enhanced apoptosis and transcriptional modulation of metabolic signaling components. These findings suggest a potential chemosensitizing role for irisin, warranting further validation at the protein and functional levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijabmr.ijabmr_477_25","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:00:19Z","timestamp":1781622019000},"page":"98-107","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Irisin Potentiates 5-fluorouracil Cytotoxicity in HT-29 Colon Cancer Cells through Enhanced Apoptosis and Transcriptional Modulation of Adenosine Monophosphate-activated Protein Kinase\/Mammalian Target of Rapamycin Signaling"],"prefix":"10.4103","volume":"16","author":[{"given":"Bassem","family":"Refaat","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"R1-20260617","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"R2-20260617","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1186\/s12885-025-15138-0","article-title":"Global burden of colorectal cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN","volume":"25","author":"Wu","year":"2025","journal-title":"BMC Cancer"},{"key":"R3-20260617","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/cancers16081530","article-title":"Colorectal cancer: Epidemiology, risk factors, and prevention","volume":"16","author":"Roshandel","year":"2024","journal-title":"Cancers (Basel)"},{"key":"R4-20260617","first-page":"111","article-title":"Nutrition, environment, and genetics in colorectal cancer","volume":"14","author":"Brandolino","year":"2025","journal-title":"Epigenetics and possible future perspective. 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