{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:56:25Z","timestamp":1768535785884,"version":"3.49.0"},"reference-count":76,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2014\/13\/D\/NZ3\/02825"],"award-info":[{"award-number":["2014\/13\/D\/NZ3\/02825"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma multiforme therapy remains a significant challenge since there is a lack of effective treatment for this cancer. As most of the examined gliomas express or overexpress cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptors \u03b3 (PPAR\u03b3), we decided to use these proteins as therapeutic targets. Toxicity, antiproliferative, proapoptotic, and antimigratory activity of COX-2 inhibitor (celecoxib\u2014CXB) and\/or PPAR\u03b3 agonist (Fmoc-L-Leucine\u2014FL) was examined in vitro on temozolomide resistant U-118 MG glioma cell line and comparatively on BJ normal fibroblasts and immortalized HaCaT keratinocytes. The in vivo activity of both agents was studied on C. elegans nematode. Both drugs effectively destroyed U-118 MG glioma cells via antiproliferative, pro-apoptotic, and anti-migratory effects in a concentration range 50\u2013100 \u00b5M. The mechanism of action of CXB and FL against glioma was COX-2 and PPAR\u03b3 dependent and resulted in up-regulation of these factors. Unlike reports by other authors, we did not observe the expected synergistic or additive effect of both drugs. Comparative studies on normal BJ fibroblast cells and immortalized HaCaT keratinocytes showed that the tested drugs did not have a selective effect on glioma cells and their mechanism of action differs significantly from that observed in the case of glioma. HaCaTs did not react with concomitant changes in the expression of COX-2 and PPAR\u03b3 and were resistant to FL. Safety tests of repurposing drugs used in cancer therapy tested on C. elegans nematode indicated that CXB, FL, or their mixture at a concentration of up to 100 \u00b5M had no significant effect on the entire nematode organism up to 4th day of incubation. After a 7-day treatment, CXB significantly shortened the lifespan of C. elegans at 25\u2013400 \u00b5M concentration and body length at 50\u2013400 \u00b5M concentration.<\/jats:p>","DOI":"10.3390\/ijms25063226","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:14:40Z","timestamp":1710245680000},"page":"3226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Repurposed Drugs Celecoxib and Fmoc-L-Leucine Alone and in Combination as Temozolomide-Resistant Antiglioma Agents\u2014Comparative Studies on Normal and Immortalized Cell Lines, and on C. elegans"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-0777","authenticated-orcid":false,"given":"\u0141ukasz","family":"Uram","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, Rzesz\u00f3w University of Technology, 6 Powsta\u0144cow Warszawy Ave., 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Pie\u0144kowska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Rzesz\u00f3w, Kopisto 2a, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Misiorek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Rzesz\u00f3w University of Technology, 6 Powsta\u0144cow Warszawy Ave., 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017baneta","family":"Szymaszek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Rzesz\u00f3w University of Technology, 6 Powsta\u0144cow Warszawy Ave., 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Twardowska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Rzesz\u00f3w University of Technology, 6 Powsta\u0144cow Warszawy Ave., 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Siorek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Rzesz\u00f3w University of Technology, 6 Powsta\u0144cow Warszawy Ave., 35-959 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-9350","authenticated-orcid":false,"given":"Stanis\u0142aw","family":"Wo\u0142owiec","sequence":"additional","affiliation":[{"name":"Medical College, University of Rzesz\u00f3w, 1a Warzywna Street, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/noac202","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015\u20132019","volume":"24","author":"Ostrom","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Weis, S., Sonnberger, M., Dunzinger, A., Voglmayr, E., Aichholzer, M., Kleiser, R., and Strasser, P. 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