{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:19:35Z","timestamp":1777393175745,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"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>Tricholoma terreum, a mushroom rich in bioactive compounds, exhibits notable antioxidant and anticancer properties. Despite its traditional use, its effects on breast cancer metabolism remain underexplored. Here, we conducted comprehensive phytochemical and volatile organic compound profiling of T. terreum extracts and evaluated their cytotoxicity against MCF-7 breast cancer cells. Using SPME\u2013GC\u2013MS and HPLC, we identified a complex chemical matrix dominated by organic acids (acetic acid, 43.85%) and nitrogen-containing heterocyclics (2-acetylpyridine, 15.19%), alongside significant phenolic acids such as gallic acid and syringic acid. Biological assays indicated that the ethanol extract showed notable cytotoxic effects, reducing MCF-7 cell viability to 3.64% after 72 h, while higher viability was preserved in healthy CCD-1072sk fibroblast cells. Using cell viability assays, flow cytometry, and gene expression analysis, we found that ethanol extracts selectively reduced cancer cell viability, induced G0\/G1 cell cycle arrest (71.92%), and promoted apoptosis. Mechanistically, treatment downregulated key nucleotide biosynthesis genes (DHFR, TK1) and the glycolytic enzyme gene (ENO1), while upregulating the oxidative stress response gene SLC7A11 (18.32-fold), suggesting disruption of cancer metabolic pathways. These findings reveal a metabolic reprogramming effect of T. terreum extracts, highlighting their potential as metabolism-targeted agents in breast cancer therapy. Further studies are warranted to validate these effects in vivo and isolate active constituents.<\/jats:p>","DOI":"10.3390\/ijms27083626","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional Reprogramming of Cancer Metabolism: Tricholoma terreum Inhibits Nucleotide Biosynthesis and Energy Flux in MCF-7 Cells by Downregulating DHFR, TK1, and ENO1"],"prefix":"10.3390","volume":"27","author":[{"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":"Faculty of Medicine, Department of Basic Medical Sciences, 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":"Faculty of Medicine, Department of Basic Medical Sciences, 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, Division of Biochemistry, Faculty of Pharmacy, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"\u017divkovi\u0107, J., Ivanov, M., Stojkovi\u0107, D., and Glamo\u010dlija, J. 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