{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:00:34Z","timestamp":1778644834744,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: This study aimed to investigate the phytochemical composition, antioxidant capacity, and anticancer potential of methanol and ethanol extracts of Lactarius deliciosus (L.) Gray in MCF-7 breast cancer cells, focusing on their effects on energy metabolism and related molecular mechanisms. Methods: In L. deliciosus samples, total antioxidant activity and total phenolic content were determined spectrophotometrically, while individual phenolics were classified by HPLC and volatile aromatic compounds (VOCs) were determined by GC-MS. The anticancer effects of L. deliciosus in MCF-7 breast cancer were determined using RT-qPCR with 46 different genes. Results: Phytochemical profiling via HPLC and GC\u2013MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 \u00b5g\/g), vanillic acid (191.98 \u00b5g\/g), and succinic acid (724.73 \u00b5g\/g). The extracts exhibited robust antioxidant activity and dose-dependent cytotoxicity, reducing cell viability to as low as 5.60% after 72 h. Molecular analysis through Reactome pathway enrichment and expression profiling of 46 genes demonstrated that L. deliciosus drives cancer cells into a metabolic impasse by reversing the Warburg effect. Key findings include the significant downregulation of glycolytic genes like SLC2A1\/GLUT1 (\u221212.34) and HK2 (\u22121.71), alongside the repression of mitochondrial TCA cycle regulators such as IDH1 (\u221217.81) and OGDH (\u22122.54). This metabolic collapse triggered G0\/G1 phase cell cycle arrest and induced apoptosis. Conlusions: These results align with international benchmarks for Lactarius species while providing novel insights into the metabolic reprogramming mechanism. The results obtained in this study highlight that L. deliciosus emerges as a promising natural agent for therapeutic strategies targeting cancer bioenergetics.<\/jats:p>","DOI":"10.3390\/nu18061008","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"1008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Phytochemical Characterization to Energy Metabolism-Driven Molecular Responses: The Anticancer Potential of Lactarius deliciosus (L.) Gray in Breast Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-1664","authenticated-orcid":false,"given":"Levent","family":"G\u00fcl\u00fcm","sequence":"first","affiliation":[{"name":"Department of Plant and Animal Production, Mudurnu S\u00fcreyya Astarc\u0131 Vocational College, Bolu Abant \u0130zzet Baysal University, Bolu 14030, T\u00fcrkiye"},{"name":"Medicinal and Aromatic Plants Research Group, Innovative Food Technologies Development Application and Research Center, Bolu Abant Izzet Baysal University, Bolu 14030, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-1651","authenticated-orcid":false,"given":"Emrah","family":"G\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Horticulture, Faculty of Agriculture, Bolu Abant \u0130zzet Baysal University, Bolu 14030, T\u00fcrkiye"},{"name":"Horticulture and Post-Harvest Research Group, Innovative Food Technologies Development Application and Research Center, Bolu Abant Izzet Baysal University, Bolu 14030, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-7623","authenticated-orcid":false,"given":"Emir","family":"\u00c7apk\u0131no\u011flu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34638, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7771-2414","authenticated-orcid":false,"given":"Ay\u015fe B\u00fc\u015franur","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Medicine, Division of Biochemistry, Recep Tayyip Erdogan University, Rize 53020, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-9644","authenticated-orcid":false,"given":"Yusuf","family":"Tutar","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Medicine, Division of Biochemistry, Recep Tayyip Erdogan University, Rize 53020, T\u00fcrkiye"},{"name":"Molecular Oncology Program, Health Sciences Institute, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"},{"name":"Molecular Medicine Program, Health Sciences Institute, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"},{"name":"Rize Training and Research Hospital, Recep Tayyip Erdogan University, Rize 53020, T\u00fcrkiye"},{"name":"Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Division of Biochemistry, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Truong, T.T., Singh, A.A., Tak, S., Na, S., Choi, J., Oh, J., and Mondal, S. 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