Evaluation of Anticancer Potential of Ganoderma lucidum on MCF-7 Breast Cancer Cells Through Genetic Transcription of Energy Metabolism

<i>Ganoderma lucidum</i> has long been recognized for its medicinal properties, particularly due to its antioxidant, anti-inflammatory, and pro-apoptotic components such as polysaccharides and triterpenoids. This study aimed to evaluate the cytotoxic and molecular effects of ethanol and methanol extracts of <i>G. lucidum</i> 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 µg/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 (-)-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 <i>ACAT1</i>, <i>ADCY3</i>, and <i>NME2,</i> key regulators of energy metabolism and epigenetic modification. On the other hand, doxorubicin treatment upregulated <i>ACAT1</i> and <i>ADCY3</i>, while a slight downregulation was observed in <i>NME2</i>. These molecular changes suggest that <i>G. lucidum</i> induces apoptosis and impairs cancer cell proliferation through metabolic disruption and gene modulation.