{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:40:00Z","timestamp":1770270000485,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Medical University of Silesia, Katowice, Poland","award":["BNW-1-040\/K\/4\/I"],"award-info":[{"award-number":["BNW-1-040\/K\/4\/I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with its development closely linked to dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways. Background: Dual-specificity phosphatases (DUSPs), as key regulators of MAPKs, play a crucial role in maintaining the balance between proliferation and apoptosis. Methods: In this study, we investigated the effect of mesalazine (MES) on the expression and activity of selected DUSP family members in normal colon epithelial cells (CCD-841CoN) and colorectal cancer cells (DLD-1). Results: Microarray analysis identified 24 transcripts with altered expression upon mesalazine treatment. The number of significantly regulated genes decreased with increasing fold-change (FC) thresholds, from 20 genes (FC &gt; 1.1) to 13 (FC &gt; 1.5) and 5 (FC &gt; 2.0), all with p &lt; 0.001. Among the DUSP genes, DUSP4 and DUSP5 showed the most pronounced and cell-type-dependent modulation. Mesalazine upregulated DUSP4 and DUSP5 expression in DLD-1 cells (p &lt; 0.001), while reducing their expression in normal CCD-841CoN cells. ELISA confirmed a 1.56-fold increase in DUSP5 protein concentration in mesalazine-treated cancer cells compared with controls (p &lt; 0.001). Conclusions: These findings suggest that mesalazine differentially modulates DUSP gene expression in normal and malignant colon epithelial cells, potentially contributing to its antiproliferative and pro-apoptotic effects through the regulation of MAPK signaling. These results provide new insights into the molecular mechanisms underlying the anticancer effects of mesalazine in colorectal cancer.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010029","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:50:21Z","timestamp":1766710221000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mesalazine Regulates DUSP1, DUSP4, and DUSP5 Expression in Colorectal Cancer: In Vitro and Bioinformatic Evidence"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-3149","authenticated-orcid":false,"given":"Marcel","family":"Madej","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Silesia LabMed, Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3742-0914","authenticated-orcid":false,"given":"Ilona","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Silesia LabMed, Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-2569","authenticated-orcid":false,"given":"Barbara","family":"Strza\u0142ka-Mrozik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-7006","authenticated-orcid":false,"given":"Magdalena","family":"Kimsa-Dudek","sequence":"additional","affiliation":[{"name":"Department of Nutrigenomics and Bromatology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-6289","authenticated-orcid":false,"given":"Celina","family":"Kruszniewska-Rajs","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3089-0409","authenticated-orcid":false,"given":"Joanna Magdalena","family":"Gola","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41392-024-01953-7","article-title":"Signaling Pathways Involved in Colorectal Cancer: Pathogenesis and Targeted Therapy","volume":"9","author":"Li","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000543921","article-title":"Colorectal Cancer: Epidemiology, Risk Factors, and Public Health Strategies","volume":"106","author":"Matsuda","year":"2025","journal-title":"Digestion"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1101\/gad.348226.120","article-title":"Genetic and Biological Hallmarks of Colorectal Cancer","volume":"35","author":"Li","year":"2021","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s10555-023-10158-3","article-title":"Colorectal Cancer: A Comprehensive Review of Carcinogenesis, Diagnosis, and Novel Strategies for Classified Treatments","volume":"43","author":"Abedizadeh","year":"2024","journal-title":"Cancer Metastasis Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zygulska, A.L., and Pierzchalski, P. (2022). Novel Diagnostic Biomarkers in Colorectal Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020852"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.5114\/aoms\/167480","article-title":"Preventive Effects of 13 Different Drugs on Colorectal Cancer: A Network Meta-Analysis","volume":"19","author":"Fu","year":"2023","journal-title":"Arch. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, R., Cheng, L., Wang, Q., and Zhou, L. (2021). Comparative Transcriptomic Analysis Reveals the Immunosuppressive Targets of Mesalazine in Dextran Sulfate Sodium-Induced Ulcerative Colitis. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.698983"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, R., Huang, X., Yang, L., Liang, X., Huang, W., Lai, K.P., and Zhou, L. (2022). Integrated Analysis Reveals the Targets and Mechanisms in Immunosuppressive Effect of Mesalazine on Ulcerative Colitis. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.867692"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3109\/1354750X.2013.819038","article-title":"DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in MAPK activation, regardless of the genotype","volume":"18","author":"Tian","year":"2013","journal-title":"Biomarkers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.3892\/ol.2016.5328","article-title":"Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis","volume":"12","author":"Yan","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"S\u0142oka, J., Strza\u0142ka-Mrozik, B., Kubica, S., Nowak, I., and Kruszniewska-Rajs, C. (2025). Influence of Mesalazine on Ferroptosis-Related Gene Expression in In Vitro Colorectal Cancer Culture. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010219"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.3802\/jgo.2017.28.e83","article-title":"Identification of DNA methylation associated gene signatures in endometrial cancer via integrated analysis of DNA methylation and gene expression systematically","volume":"28","author":"Men","year":"2017","journal-title":"J. Gynecol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112543","DOI":"10.1016\/j.biopha.2021.112543","article-title":"Mesalazine initiates an anti-oncogenic \u03b2-catenin \/ MUCDHL negative feed-back loop in colon cancer cells by cell-specific mechanisms","volume":"146","author":"Bersuder","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1046\/j.1365-2036.18.s2.1.x","article-title":"Review article: Mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease","volume":"18","author":"Allgayer","year":"2003","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"S\u0142oka, J., Madej, M., and Strza\u0142ka-Mrozik, B. (2023). Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules, 28.","DOI":"10.3390\/molecules28135081"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1111\/j.1572-0241.2000.03360.x","article-title":"Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis","volume":"95","author":"Bantel","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/carcin\/bgab077","article-title":"CDKN2B antisense RNA 1 suppresses tumor growth in human colorectal cancer by targeting MAPK inactivator dual-specificity phosphatase 1","volume":"42","author":"Pan","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S1470-2045(05)70168-6","article-title":"The MAPK signalling pathways and colorectal cancer","volume":"6","author":"Fang","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.3748\/wjg.14.4434","article-title":"Molecular basis of the potential of mesalazine to prevent colorectal cancer","volume":"14","author":"Stolfi","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1053\/j.gastro.2009.10.038","article-title":"Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis","volume":"138","author":"Brown","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"738","DOI":"10.7150\/ijms.24981","article-title":"The suppression of DUSP5 expression correlates with paclitaxel resistance and poor prognosis in basal-like breast cancer","volume":"15","author":"Liu","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_22","first-page":"4186","article-title":"Down-regulation of dual-specificity phosphatase 5 predicts poor prognosis of patients with prostate cancer","volume":"8","author":"Cai","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_23","first-page":"1116","article-title":"LncRNA ROR1-AS1 promotes colon cancer cell proliferation by suppressing the expression of DUSP5\/CDKN1A","volume":"24","author":"Wang","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/s41419-022-05499-w","article-title":"BAF53A drives colorectal cancer development by regulating DUSP5-mediated ERK phosphorylation","volume":"13","author":"Yang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Buffet, C., Hecale-Perlemoine, K., Bricaire, L., Dumont, F., Baudry, C., Tissier, F., Bertherat, J., Cochand-Priollet, B., Raffin-Sanson, M.-L., and Cormier, F. (2017). DUSP5 and DUSP6, two ERK specific phosphatases, are markers of a higher MAPK signaling activation in BRAF mutated thyroid cancers. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184861"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1038\/s41598-018-20176-9","article-title":"DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis","volume":"8","author":"Nightingale","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:36:51Z","timestamp":1766986611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,25]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["pharmaceutics18010029"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18010029","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,25]]}}}