{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:54:37Z","timestamp":1783702477111,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gliomas are among the most challenging brain tumors to treat, owing to their marked heterogeneity and the aberrant signaling networks that sustain tumor growth and resistance to therapy. Quercetin, a dietary flavonoid widely found in fruit and vegetables, exhibits documented anticancer activity, prompting the development of optimized derivatives with improved biological potency. In earlier work, we synthesized and evaluated a series of quercetin derivatives and identified the acylated compound 3-O-decanoylquercetin (Q-3-Dec) as particularly effective in reducing glioma cell viability. In this study, we explored Q-3-Dec as a multi-target agent, which concomitantly impairs NF-\u03baB\/STAT3-dependent survival signaling, mitochondrial function, and O6-Methylguanine-DNA Methyltransferase (MGMT) expression, a DNA repair enzyme closely associated with chemoresistance, in glioma cells. In U373-MG glioma cells, treatment with 50 \u03bcM Q-3-Dec triggered pronounced, time-dependent morphological changes and an early loss of mitochondrial membrane potential after 3 h. With prolonged exposure, Q-3-Dec markedly decreased NF-\u03baB and STAT3 phosphorylation and reduced the expression of the anti-apoptotic proteins Bcl-2 and survivin, alongside a significant decrease in MGMT levels. These combined effects culminated in a progressive increase in cell death, reaching approximately 30% after 48 h. Together, these findings position Q-3-Dec as a multi-node modulator of glioma survival, supporting its potential for further preclinical development to improve future therapeutic strategies against glioma.<\/jats:p>","DOI":"10.3390\/ijms27041726","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:15:12Z","timestamp":1770801312000},"page":"1726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pleiotropic Effects of 3-O-Decanoylquercetin on U373-MG Human Glioma Cell Line"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4349-0276","authenticated-orcid":false,"given":"Paola","family":"Dell\u2019Albani","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"La Cognata","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-439X","authenticated-orcid":false,"given":"Sebastiano Alfio","family":"Torrisi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-056X","authenticated-orcid":false,"given":"Andrea","family":"De Gaetano","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Via P. Gaifami, 18, 95126 Catania, Italy"},{"name":"Institute for Systems Analysis and Computer Science \u201cA. Ruberti\u201d (IASI), BioMatLab (Biomathematics Laboratory), National Research Council of Italy (CNR), 00185 Rome, Italy"},{"name":"Department of Mathematics, Mahidol University, Bangkok 10400, Thailand"},{"name":"Department of Biomatics, \u00d3buda University, 1034 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Concetto","family":"Foti","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry (ICB), National Research Council of Italy (CNR), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/jnen\/61.3.215","article-title":"The WHO classification of tumors of the nervous system","volume":"61","author":"Kleihues","year":"2002","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jconrel.2023.04.020","article-title":"A review on in vitro model of the blood-brain barrier (BBB) based on hCMEC\/D3 cells","volume":"358","author":"Qi","year":"2023","journal-title":"J. Control. 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