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Natural antioxidants such as glycosylated delphinidins\u2014anthocyanins abundant in Chilean berries, particularly the native species Aristotelia chilensis (maqui)\u2014have emerged as bioactive compounds that modulate inflammation and cancer-related pathways. In this context, the regulation of inflammation-associated signaling pathways, including COX-2 and NF-\u03baB, represents a potential strategy to overcome chemoresistance. In this study, we evaluated the effect of delphinidin-3-glucoside (DEL-3) on the COX-2\/PGE2 axis, MDR1 expression, and sensitivity to chemotherapeutic agents in U87-MG and GBM38 glioblastoma cells and in an NOD-SCID xenograft model using ELISA, RT-qPCR, Western blot, and luciferase reporter assays. DEL-3 reduced PGE2 production, consistent with functional modulation of the COX-2\/PGE2 pathway, and downregulated MDR1 expression at both transcriptional and protein levels, in agreement with reduced promoter activity. Functionally, combined treatment with DEL-3 and MDR1-substrate chemotherapeutic agents enhanced cytotoxicity in U87-MG cells. Although DEL-3 did not significantly reduce tumor growth in a NOD-SCID xenograft model, MDR1 expression was reduced in treated tumors, indicating in vivo modulation of the target. Overall, these findings suggest that DEL-3, as a natural antioxidant, modulates inflammation-associated mechanisms and downregulates MDR1, thereby potentially enhancing the sensitivity of glioblastoma cells to MDR1-substrate chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/antiox15081005","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycosylated Delphinidins, Natural Antioxidants, Functionally Modulate the COX-2\/PGE2 Axis and Downregulate MDR1 in Glioblastoma Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Constanza","family":"Cuevas","sequence":"first","affiliation":[{"name":"Laboratorio de Oncovirolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"},{"name":"Laboratorio de Biolog\u00eda Tumoral, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yessica","family":"Nahuelpan","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncovirolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darling","family":"Haro","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncovirolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, 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Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"P\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncovirolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Garcia-Romero","sequence":"additional","affiliation":[{"name":"Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain"},{"name":"Brain Tumour Laboratory, Fundaci\u00f3n Vithas, Grupo Hospitales Vithas, 28223 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Ayuso-Sacido","sequence":"additional","affiliation":[{"name":"Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain"},{"name":"Brain Tumour Laboratory, Fundaci\u00f3n Vithas, Grupo Hospitales Vithas, 28223 Madrid, 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