From Phytochemical Characterization to Energy Metabolism-Driven Molecular Responses: The Anticancer Potential of Lactarius deliciosus (L.) Gray in Breast Cancer Cells

<b>Background/Objectives</b>: This study aimed to investigate the phytochemical composition, antioxidant capacity, and anticancer potential of methanol and ethanol extracts of <i>Lactarius deliciosus</i> (L.) Gray in MCF-7 breast cancer cells, focusing on their effects on energy metabolism and related molecular mechanisms. <b>Methods:</b> In <i>L. deliciosus</i> 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 <i>L. deliciosus</i> in MCF-7 breast cancer were determined using RT-qPCR with 46 different genes. <b>Results:</b> Phytochemical profiling via HPLC and GC-MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 µg/g), vanillic acid (191.98 µg/g), and succinic acid (724.73 µg/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 <i>L. deliciosus</i> drives cancer cells into a metabolic impasse by reversing the Warburg effect. Key findings include the significant downregulation of glycolytic genes like <i>SLC2A1</i>/<i>GLUT1</i> (-12.34) and <i>HK2</i> (-1.71), alongside the repression of mitochondrial TCA cycle regulators such as <i>IDH1</i> (-17.81) and <i>OGDH</i> (-2.54). This metabolic collapse triggered G0/G1 phase cell cycle arrest and induced apoptosis. <b>Conlusions</b>: These results align with international benchmarks for <i>Lactarius</i> species while providing novel insights into the metabolic reprogramming mechanism. The results obtained in this study highlight that <i>L. deliciosus</i> emerges as a promising natural agent for therapeutic strategies targeting cancer bioenergetics.