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

Abstract

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-MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 & micro;g/g), vanillic acid (191.98 & micro;g/g), and succinic acid (724.73 & micro;g/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 (-12.34) and HK2 (-1.71), alongside the repression of mitochondrial TCA cycle regulators such as IDH1 (-17.81) and OGDH (-2.54). 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.