168377 20260204153543.0 doi 10.3390/antiox14121452 sideral 147838 ART-2025-147838 eng Bidooki, Seyed Hesamoddin Universidad de Zaragoza Lactarius deliciosus extract from green microwave-assisted eutectic solvent extraction as a therapeutic candidate against colon cancer 2025 Lactarius deliciosus is a widely distributed edible mushroom valued as a functional food due to its rich content of nutrients, phenolic compounds, and flavonoids, which contribute to its strong antioxidant and antimicrobial properties. The present study aimed to optimize a green microwave-assisted extraction method for maximal recovery of bioactive phenolic compounds from Lactarius deliciosus extract (LDE) and to evaluate its antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects on human colon carcinoma (Caco-2) cells. The study demonstrated that solvent polarity and composition critically influence the recovery of antioxidant biomolecules, identifying water and NaDES 1 (glycerol/glycine/water) as the most efficient and sustainable solvents for microwave-assisted extraction at 225 °C. The LDE showed high levels of phenolic compounds—particularly 4-hydroxybenzoic and vanillic acids—indicating potent antioxidant potential and possible anticancer efficacy. The results revealed that the LDE significantly reduced colony formation and cell adhesion in a dose-dependent manner, leading to nearly complete inhibition of clonogenic survival at the IC50 concentration and a marked increase in cell death among non-adherent colon cancer cells. In addition, LDE inhibited the proliferation of Caco-2 cells by inducing G0/G1 cell cycle arrest and apoptosis, associated with altered mitochondrial potential and increased caspase-3 activity. The LDE modified the redox balance of the cell by decreasing the ROS levels and exerts anti-inflammatory effects through significant downregulation of NOS2 expression, without adversely affecting the intestinal barrier. The study concludes that LDE bioactive compounds show strong promise as anticancer and functional ingredients, demonstrating antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012 info:eu-repo/grantAgreement/ES/DGA/B16-23R info:eu-repo/grantAgreement/ES/DGA/GCP-2018-002300 info:eu-repo/grantAgreement/ES/MCINN/PID2022-136414OB-I00 info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEWPOWER-S1-1.1-E01116 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rodríguez-Martínez, Beatriz Quero, Javier Herrera-Marcos, Luis Vicente Universidad de Zaragoza (orcid)0000-0002-4665-9674 Paesa, Mónica Universidad de Zaragoza Delgado-Machuca, Marina Beas-Guzmán, Oscar F. Osada, Jesús Universidad de Zaragoza (orcid)0000-0002-8251-8457 Ferreira-Santos, Pedro Rodríguez-Yoldi, María Jesús Universidad de Zaragoza (orcid)0000-0002-3595-7668 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 14, 12 (2025), 1452 [21 pp.] Antioxidants Antioxidants 2076-3921 2464099 http://zaguan.unizar.es/record/168377/files/texto_completo.pdf Versión publicada 2877421 http://zaguan.unizar.es/record/168377/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:168377 articulos driver 2026-02-04-13:14:49 ARTICLE