{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:24:09Z","timestamp":1770967449143,"version":"3.50.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glioblastoma (GB) is the most aggressive primary glioma, with a median survival of 15-18 months. Current treatments are often ineffective, largely due to tumor heterogeneity and recurrence. Advances in understanding GB\u2019s molecular landscape and microenvironment have highlighted new therapeutic strategies to fight this life-threatening tumor. Given the pivotal role of natural compounds in drug discovery, those with anti-inflammatory and cytotoxic\/cytostatic properties are emerging as promising candidates for GB therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigates the antitumor and immunomodulatory effects of 7\u03b1-acetoxy-6\u03b2-hydroxyroyleanone (Roy), a diterpene isolated by our team from Plectranthus hadiensis Schweinf., using both 2D and 3D GB cell models. U87 cells were used as a standard GB model and to generate monocellular and multicellular spheroids (U87, HMC3, and\/or HBMEC cells). Both models were treated with 16 \u00b5M of Roy, a concentration previously shown to be tumor-specific.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Roy significantly reduced spheroid size and metabolic activity over time, with the most pronounced effects observed in multicellular spheroids. This compound also inhibited cell proliferation by preventing colony formation and downregulating CDK4 and VEGFA mRNA levels. Roy\u2019s bioactivity was enhanced in the presence of conditioned medium (secretome from GB and\/or microglia cells), exerting a neuromodulatory effect by modulating IL6\/JAK2\/STAT3 mRNA expression and by suppressing the secretion of cytokines involved in the chronic inflammatory state within the GB microenvironment. Importantly, Roy was also able to cross the blood-brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings, in line with our previous work, underscore the cytotoxic potential of this natural compound, suggesting Roy as a promising lead candidate for future GB treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1728792","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:39:22Z","timestamp":1770964762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["7\u03b1-acetoxy-6\u03b2-hydroxyroyleanone (Roy) modulates IL-6\/STAT3\/JAK2 mRNA expression and suppresses tumor growth in glioblastoma cell models"],"prefix":"10.3389","volume":"17","author":[{"given":"Mariana","family":"Magalh\u00e3es","sequence":"first","affiliation":[{"name":"PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research, University of Coimbra","place":["Coimbra, Portugal"]},{"name":"CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra","place":["Coimbra, Portugal"]},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, University of Coimbra","place":["Coimbra, Portugal"]},{"name":"CiBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra","place":["Coimbra, Portugal"]}]},{"given":"Renato","family":"Spigarelli","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna","place":["Bologna, Italy"]}]},{"given":"Eva Mar\u00eda","family":"Dom\u00ednguez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Universidad de Alcala, Facultad de Farmacia, Departamento de Ciencias Biom\u00e9dicas e Instituto de Investigaci\u00f3n Qu\u00edmica \u201cAndr\u00e9s M. del R\u00edo\u201d (IQAR), \u00c1rea de Farmacolog\u00eda, Grupos \u201cDise\u00f1o, interacci\u00f3n y s\u00edntesis de compuestos biol\u00f3gicamente activos (DISCOBAC)\u201d y \u201cBases moleculares de la resistencia en c\u00e1ncer (CARE)\u201d, Ctra. 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