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This study aimed to evaluate the cytotoxic and molecular effects of ethanol and methanol extracts of G. lucidum as well as doxorubicin on MCF-7 breast cancer cells. The cytotoxicity was assessed via MTT assay. The methanol extract showed stronger cytotoxicity (IC50: 62.37 \u00b5g\/mL) than the ethanol extract, while doxorubicin exhibited an IC50 value of 0.66 mM. Phenolic profiling by HPLC revealed high levels of vanillic acid, gallic acid and (\u2212)-epicatechin in the methanol extract, while volatile compounds such as hexanal and acetic acid were identified by GC-MS. Flow cytometric analysis demonstrated G0\/G1 phase cell cycle arrest and an increase in early and late apoptotic populations. Gene expression studies using RT-qPCR showed significant downregulation of ACAT1, ADCY3, and NME2, key regulators of energy metabolism and epigenetic modification. On the other hand, doxorubicin treatment upregulated ACAT1 and ADCY3, while a slight downregulation was observed in NME2. These molecular changes suggest that G. lucidum induces apoptosis and impairs cancer cell proliferation through metabolic disruption and gene modulation.<\/jats:p>","DOI":"10.3390\/antiox14121471","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"1471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of Anticancer Potential of Ganoderma lucidum on MCF-7 Breast Cancer Cells Through Genetic Transcription of Energy Metabolism"],"prefix":"10.3390","volume":"14","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, Turkey"},{"name":"Medicinal and Aromatic Plants Research Group, Innovative Food Technologies Development Application and Research Center, Bolu Abant Izzet Baysal University, Bolu 14030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7771-2414","authenticated-orcid":false,"given":"Ay\u015fe B\u00fc\u015franur","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-9644","authenticated-orcid":false,"given":"Yusuf","family":"Tutar","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Division of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53020, Turkey"},{"name":"Department of Basic Pharmaceutical Sciences, Division of Biochemistry, Faculty of Pharmacy, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Ye, X., Liu, Y., Cui, C., Shi, S., Wu, H., Tian, H., Song, D., Yao, J., and Wang, L. 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